Different Faces of the Heme-Heme Oxygenase System in Inflammation

The heme-heme oxygenase system has recently been recognized to possess important regulatory properties. It is tightly involved in both physiological as well as pathophysiological processes, such as cytoprotection, apoptosis, and inflammation. Heme functions as a double-edged sword. In moderate quantities and bound to protein, it forms an essential element for various biological processes, but when unleashed in large amounts, it can become toxic by mediating oxidative stress and inflammation. The effect of this free heme on the vascular system is determined by extracellular factors, such as hemoglobin/heme-binding proteins, haptoglobin, albumin, and hemopexin, and intracellular factors, including heme oxygenases and ferritin. Heme oxygenase (HO) enzyme activity results in the degradation of heme and the production of iron, carbon monoxide, and biliverdin. All these heme-degradation products are potentially toxic, but may also provide strong cytoprotection, depending on the generated amounts and the microenvironment. Pre-induction of HO activity has been demonstrated to ameliorate inflammation and mediate potent resistance to oxidative injury. A better understanding of the complex heme-heme

[1]  D. Willis Expression and modulatory effects of heme oxygenase in acute inflammation in the rat , 1995, Inflammation Research.

[2]  J. Reichen,et al.  The effect of hypoxia on hepatic cytochromes and heme turnover in rats in vivo , 1988, Experientia.

[3]  R. Virchow Die pathologischen Pigmente , 1847, Archiv für pathologische Anatomie und Physiologie und für klinische Medicin.

[4]  W. Walden,et al.  Characteristics of the interaction of the ferritin repressor protein with the iron-responsive element , 2005, Biology of Metals.

[5]  P. Manoharan,et al.  Redox reactions of hemoglobin. , 2004, Antioxidants & redox signaling.

[6]  D. Shemin On the synthesis of heme , 1970, Naturwissenschaften.

[7]  C. Figdor,et al.  The heme-heme oxygenase system: a molecular switch in wound healing. , 2003, Blood.

[8]  C. Ricordi,et al.  Heme oxygenase-1 fused to a TAT peptide transduces and protects pancreatic β-cells , 2003 .

[9]  C. Ricordi,et al.  Heme oxygenase-1 fused to a TAT peptide transduces and protects pancreatic beta-cells. , 2003, Biochemical and biophysical research communications.

[10]  A. Choi,et al.  Regulation of IL-1beta -induced GM-CSF production in human airway smooth muscle cells by carbon monoxide. , 2003, American journal of physiology. Lung cellular and molecular physiology.

[11]  Fang Liu,et al.  Carbon monoxide modulates endotoxin-induced production of granulocyte macrophage colony-stimulating factor in macrophages. , 2002, American journal of respiratory cell and molecular biology.

[12]  Solomon H. Snyder,et al.  Biliverdin reductase: A major physiologic cytoprotectant , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[13]  F. Gao,et al.  Heme oxygenase 1 mediates the immunomodulatory and antiapoptotic effects of interleukin 13 gene therapy in vivo and in vitro. , 2002, Human gene therapy.

[14]  H. Volk,et al.  Inhibition of ischemia/reperfusion injury and chronic graft deterioration by a single-donor treatment with cobalt-protoporphyrin for the induction of heme oxygenase-1 , 2002, Transplantation.

[15]  J. Eaton,et al.  Pro-oxidant and cytotoxic effects of circulating heme. , 2002, Blood.

[16]  A. Choi,et al.  Heme oxygenase-1: the "emerging molecule" has arrived. , 2002, American journal of respiratory cell and molecular biology.

[17]  F. Bach,et al.  Heme Oxygenase-1-derived Carbon Monoxide Requires the Activation of Transcription Factor NF-κB to Protect Endothelial Cells from Tumor Necrosis Factor-α-mediated Apoptosis* , 2002, The Journal of Biological Chemistry.

[18]  F. Torti,et al.  Regulation of ferritin genes and protein. , 2002, Blood.

[19]  P. Low,et al.  Heme Redox Properties of S-Nitrosated Hemoglobin A0 and Hemoglobin S , 2002, The Journal of Biological Chemistry.

[20]  J. Donnez,et al.  Potential involvement of hemoglobin and heme in the pathogenesis of peritoneal endometriosis. , 2002, Fertility and sterility.

[21]  Li Zhang,et al.  The Molecular Chaperone Hsp90 Mediates Heme Activation of the Yeast Transcriptional Activator Hap1* , 2002, The Journal of Biological Chemistry.

[22]  P. Frenette Sickle cell vaso-occlusion: multistep and multicellular paradigm , 2002, Current opinion in hematology.

[23]  Tzong-Shyuan Lee,et al.  Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice , 2002, Nature Medicine.

[24]  J. Oyama,et al.  Gene Therapy Strategy for Long-Term Myocardial Protection Using Adeno-Associated Virus-Mediated Delivery of Heme Oxygenase Gene , 2002, Circulation.

[25]  B. Ke,et al.  Heme oxygenase-1 overexpression protects rat hearts from cold ischemia/reperfusion injury via an antiapoptotic pathway. , 2002, Transplantation.

[26]  T. Kohchi,et al.  Making light of it: the role of plant haem oxygenases in phytochrome chromophore synthesis. , 2001, Biochemical Society transactions.

[27]  Y. Oda,et al.  Heme oxygenase-1 deficiency: the first autopsy case. , 2002, Human pathology.

[28]  N. Abraham,et al.  Regulation of cyclooxygenase by the heme-heme oxygenase system in microvessel endothelial cells. , 2002, The Journal of pharmacology and experimental therapeutics.

[29]  D. Stevenson,et al.  The Biology of Bilirubin Production , 2001, Journal of Perinatology.

[30]  J. Alam,et al.  Cellular overexpression of heme oxygenase-1 up-regulates p21 and confers resistance to apoptosis. , 2001, Kidney international.

[31]  G. Drummond,et al.  Sn-Mesoporphyrin interdiction of severe hyperbilirubinemia in Jehovah's Witness newborns as an alternative to exchange transfusion. , 2001, Pediatrics.

[32]  A. Kappas,et al.  Treatment of Hyperbilirubinemia Pharmacologic Approach SnMP(Tin-Mesoporphyrin) , 2001, Journal of Perinatology.

[33]  W. Durante,et al.  Adenovirus-Mediated Heme Oxygenase-1 Gene Delivery Inhibits Injury-Induced Vascular Neointima Formation , 2001, Circulation.

[34]  J. Lebreton,et al.  Induction of heme-oxygenase-1 prevents the systemic responses to hemorrhagic shock. , 2001, American journal of respiratory and critical care medicine.

[35]  P. Högger,et al.  Soluble CD163 inhibits phorbol ester-induced lymphocyte proliferation. , 2001, Biochemical and biophysical research communications.

[36]  C. Cho,et al.  Modulation of heme oxygenase in tissue injury and its implication in protection against gastrointestinal diseases. , 2001, Life sciences.

[37]  K. Kröncke,et al.  Nitric Oxide Inhibits Endothelial IL-1β-induced ICAM-1 Gene Expression at the Transcriptional Level Decreasing Sp1 and AP-1 Activity , 2001, Molecular medicine.

[38]  L. Fabbri,et al.  Increased expression of heme oxygenase (HO)-1 in alveolar spaces and HO-2 in alveolar walls of smokers. , 2001, American journal of respiratory and critical care medicine.

[39]  N. Abraham,et al.  Regulation of human heme oxygenase in endothelial cells by using sense and antisense retroviral constructs , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[40]  O. Wagner,et al.  Heme Oxygenase-1 Gene Promoter Microsatellite Polymorphism is Associated with Restenosis after Percutaneous Transluminal Angioplasty , 2001, Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists.

[41]  S. Snyder,et al.  Neural roles for heme oxygenase: Contrasts to nitric oxide synthase , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[42]  W. Oyen,et al.  Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase. , 2001, Blood.

[43]  S. Snyder,et al.  Heme Oxygenase: A Font of Multiple Messengers , 2001, Neuropsychopharmacology.

[44]  F. Bach,et al.  Heme oxygenase-1 induction in islet cells results in protection from apoptosis and improved in vivo function after transplantation. , 2001, Diabetes.

[45]  N. Abraham,et al.  Human Heme Oxygenase-1 Gene Transfer Lowers Blood Pressure and Promotes Growth in Spontaneously Hypertensive Rats , 2001, Hypertension.

[46]  T. Minamino,et al.  Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[47]  A. Choi,et al.  Carbon monoxide attenuates aeroallergen-induced inflammation in mice. , 2001, American journal of physiology. Lung cellular and molecular physiology.

[48]  James L. Park,et al.  Heme oxygenase-1 protects against vascular constriction and proliferation , 2001, Nature Medicine.

[49]  S Shibahara,et al.  Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1 , 2001, The EMBO journal.

[50]  F. Lyall,et al.  Heme oxygenase expression in human placenta and placental bed: reduced expression of placenta endothelial HO‐2 in preeclampsia and fetal growth restriction , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[51]  R. Cashon,et al.  Redox reactions of hemoglobin and myoglobin: biological and toxicological implications. , 2001, Antioxidants & redox signaling.

[52]  R. Hebbel,et al.  Modulation of endothelial cell activation in sickle cell disease: a pilot study. , 2001, Blood.

[53]  A. Choi,et al.  Carbon Monoxide Generated by Heme Oxygenase-1 Suppresses the Rejection of Mouse-to-Rat Cardiac Transplants1 , 2001, The Journal of Immunology.

[54]  J. Grande,et al.  Oxidative stress and induction of heme oxygenase-1 in the kidney in sickle cell disease. , 2001, The American journal of pathology.

[55]  M. Rücker,et al.  Reduction of inflammatory response in composite flap transfer by local stress conditioning-induced heat-shock protein 32. , 2001, Surgery.

[56]  C. Figdor,et al.  Heme-induced cell adhesion in the pathogenesis of sickle-cell disease and inflammation. , 2001, Trends in pharmacological sciences.

[57]  H. Volk,et al.  Induction of heme-oxygenase-1 prevents ischemia/reperfusion injury and improves long-term graft outcome in rat renal allografts. , 2001, Transplantation proceedings.

[58]  F. Robertson,et al.  Inhibition of Cutaneous UV Light–induced Tumor Necrosis Factor-α Protein Production by Allotrap 1258, a Novel Immunomodulatory Peptide¶ , 2001 .

[59]  F. Robertson,et al.  Inhibition of Cutaneous UV Light–induced Tumor Necrosis Factor‐α Protein Production by Allotrap 1258, a Novel Immunomodulatory Peptide ¶ , 2001, Photochemistry and photobiology.

[60]  I. Hochberg,et al.  Haptoglobin phenotype as a predictor of restenosis after percutaneous transluminal coronary angioplasty. , 2001, The American journal of cardiology.

[61]  S. Werner,et al.  Haem oxygenase-1: a novel player in cutaneous wound repair and psoriasis? , 2001, The Biochemical journal.

[62]  S. Moestrup,et al.  Identification of the haemoglobin scavenger receptor , 2001, Nature.

[63]  N. Traverso,et al.  Induction of heme oxygenase 1 in liver of spontaneously diabetic rats , 2001, Free radical research.

[64]  J. Alam,et al.  Heme protein-induced chronic renal inflammation: suppressive effect of induced heme oxygenase-1. , 2001, Kidney international.

[65]  M. Maines,et al.  The heme oxygenase system and cellular defense mechanisms. Do HO-1 and HO-2 have different functions? , 2001, Advances in experimental medicine and biology.

[66]  A. Choi,et al.  Heme oxygenase: colors of defense against cellular stress. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[67]  R. Hamilton,et al.  Protection against ozone-induced pulmonary inflammation and cell death by endotoxin pretreatment in mice: role of HO-1. , 2000, Inhalation toxicology.

[68]  S. Brod Unregulated inflammation shortens human functional longevity , 2000, Inflammation Research.

[69]  S. Snyder,et al.  Amyloid Precursor Proteins Inhibit Heme Oxygenase Activity and Augment Neurotoxicity in Alzheimer's Disease , 2000, Neuron.

[70]  G. Ramadori,et al.  Gene regulation of heme oxygenase-1 as a therapeutic target. , 2000, Biochemical pharmacology.

[71]  A. Choi,et al.  Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis , 2000, The Journal of experimental medicine.

[72]  K. Nath,et al.  Mechanisms underlying induction of heme oxygenase-1 by nitric oxide in renal tubular epithelial cells. , 2000, American journal of physiology. Renal physiology.

[73]  M. Buyzere,et al.  A new Method for Fast Haptoglobin Phenotyping and Hemoglobin Binding Capacity Calculation Based on Capillary Zone Electrophoresis , 2000, Clinical chemistry and laboratory medicine.

[74]  C. Cross,et al.  Nitric oxide: a pro-inflammatory mediator in lung disease? , 2000, Respiratory research.

[75]  R. Foresti,et al.  Dynamics of haem oxygenase-1 expression and bilirubin production in cellular protection against oxidative stress. , 2000, The Biochemical journal.

[76]  G. Vercellotti,et al.  Ferriporphyrins and endothelium: a 2-edged sword-promotion of oxidation and induction of cytoprotectants. , 2000, Blood.

[77]  S. Snyder,et al.  A Mammalian Iron ATPase Induced by Iron* , 2000, The Journal of Biological Chemistry.

[78]  L. McIntire,et al.  Perfusion with sickle erythrocytes up-regulates ICAM-1 and VCAM-1 gene expression in cultured human endothelial cells. , 2000, Blood.

[79]  M. Maines The heme oxygenase system and its functions in the brain. , 2000, Cellular and molecular biology.

[80]  J. Alam,et al.  The indispensability of heme oxygenase-1 in protecting against acute heme protein-induced toxicity in vivo. , 2000, The American journal of pathology.

[81]  H. Nick,et al.  Renal response to tissue injury: lessons from heme oxygenase-1 GeneAblation and expression. , 2000, Journal of the American Society of Nephrology : JASN.

[82]  D. Granger,et al.  Heme oxygenase modulates selectin expression in different regional vascular beds. , 2000, American journal of physiology. Heart and circulatory physiology.

[83]  H. Schröder,et al.  Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[84]  M. Behrend Immune-adhesion molecules in the prevention of allograft rejection and reperfusion injury , 2000, Expert opinion on investigational drugs.

[85]  P. R. Montellano The mechanism of heme oxygenase. , 2000, Current opinion in chemical biology.

[86]  D. Willis,et al.  Heme oxygenase isoform expression in cellular and antibody‐mediated models of acute inflammation in the rat , 2000, The Journal of pathology.

[87]  A. Choi,et al.  Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway , 2000, Nature Medicine.

[88]  T. Kietzmann,et al.  Transcriptional induction of heme oxygenase-1 gene expression by okadaic acid in primary rat hepatocyte cultures. , 2000, Molecular pharmacology.

[89]  B. Chatterjee,et al.  Age-dependent increase of heme oxygenase–1 gene expression in the liver mediated by NFκB , 2000, Mechanisms of Ageing and Development.

[90]  J. David Clark,et al.  Chronic morphine exposure and the expression of heme oxygenase type 2. , 2000, Brain research. Molecular brain research.

[91]  A. Choi,et al.  Heme oxygenase-1 inhibits TNF-α-induced apoptosis in cultured fibroblasts , 2000 .

[92]  M. Suematsu,et al.  Protective roles of endogenous carbon monoxide in neointimal development elicited by arterial injury. , 2000, American journal of physiology. Heart and circulatory physiology.

[93]  S. Ryter,et al.  The heme synthesis and degradation pathways: role in oxidant sensitivity. Heme oxygenase has both pro- and antioxidant properties. , 2000, Free radical biology & medicine.

[94]  M. Maines,et al.  Developmentally regulated expression of two transcripts for heme oxygenase-2 with a first exon unique to rat testis: control by corticosterone of the oxygenase protein expression. , 2000, Gene.

[95]  A. Alayash Hemoglobin-based blood substitutes and the hazards of blood radicals , 2000, Free radical research.

[96]  T. Langmann,et al.  Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro‐ and antiinflammatory stimuli , 2000, Journal of leukocyte biology.

[97]  M. Smith,et al.  Evidence for a novel heme-binding protein, HasAh, in Alzheimer disease. , 2000, Antioxidants & redox signaling.

[98]  A. Choi,et al.  Heme oxygenase-1 inhibits TNF-alpha-induced apoptosis in cultured fibroblasts. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[99]  M. Takahashi,et al.  Interaction of amyloid precursor proteins and heme oxygenase. , 2000, Alzheimer disease and associated disorders.

[100]  J Zaky,et al.  Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury. , 1999, The Journal of clinical investigation.

[101]  S. Brouard,et al.  RDP1258, a New Rationally Designed Immunosuppressive Peptide, Prolongs Allograft Survival in Rats: Analysis of Its Mechanism of Action , 1999, Molecular medicine.

[102]  R. Foresti,et al.  The heme oxygenase pathway and its interaction with nitric oxide in the control of cellular homeostasis. , 1999, Free radical research.

[103]  K. Nath Heme oxygenase-1: a redoubtable response that limits reperfusion injury in the transplanted adipose liver. , 1999, The Journal of clinical investigation.

[104]  L. Zhang,et al.  Molecular mechanism of heme signaling in yeast: the transcriptional activator Hap1 serves as the key mediator , 1999, Cellular and Molecular Life Sciences CMLS.

[105]  K. Matsumoto,et al.  Induction of heme oxygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress: role of bilirubin generated by the enzyme. , 1999, Circulation research.

[106]  N. Abraham,et al.  Differential effects of heme oxygenase isoforms on heme mediation of endothelial intracellular adhesion molecule 1 expression. , 1999, The Journal of pharmacology and experimental therapeutics.

[107]  P. Dennery,et al.  Reversal of HO‐1 related cytoprotection with increased expression is due to reactive iron , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[108]  A. Baldwin Modified hemoglobins produce venular interendothelial gaps and albumin leakage in the rat mesentery. , 1999, American journal of physiology. Heart and circulatory physiology.

[109]  S. D. Brady,et al.  Haem oxygenase-1 prevents cell death by regulating cellular iron , 1999, Nature Cell Biology.

[110]  G. Ramadori,et al.  Up‐regulation of heme‐binding protein 23 (HBP23) gene expression by lipopolysaccharide is mediated via a nitric oxide‐dependent signaling pathway in rat Kupffer cells , 1999, Hepatology.

[111]  L. Yang,et al.  Retrovirus-mediated HO gene transfer into endothelial cells protects against oxidant-induced injury. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[112]  K. Moore Cell biology of chronic wounds: the role of inflammation. , 1999, Journal of wound care.

[113]  Kazuhiro Takahashi,et al.  Suppression of Heme Oxygenase‐1 mRNA Expression by Interferon‐γ in Human Glioblastoma Cells , 1999 .

[114]  P. Sarathchandra,et al.  Peroxynitrite induces haem oxygenase-1 in vascular endothelial cells: a link to apoptosis. , 1999, The Biochemical journal.

[115]  J. Hoidal,et al.  TNF-alpha and IL-1alpha induce heme oxygenase-1 via protein kinase C, Ca2+, and phospholipase A2 in endothelial cells. , 1999, The American journal of physiology.

[116]  J. Hoidal,et al.  TNF-α and IL-1α induce heme oxygenase-1 via protein kinase C, Ca2+, and phospholipase A2 in endothelial cells. , 1999, American journal of physiology. Heart and circulatory physiology.

[117]  L. Zhang,et al.  Heme initiates changes in the expression of a wide array of genes during the early erythroid differentiation stage. , 1999, Biochemical and biophysical research communications.

[118]  A. Choi,et al.  rapid communication Carbon monoxide provides protection against hyperoxic lung injury , 2022 .

[119]  G. De Backer,et al.  Associations between haptoglobin polymorphism, lipids, lipoproteins and inflammatory variables. , 1999, Atherosclerosis.

[120]  A. Choi,et al.  Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury. , 1999, The Journal of clinical investigation.

[121]  S. Snyder,et al.  Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[122]  M. Maines,et al.  Overexpression of Heme Oxygenase‐1 Is Neuroprotective in a Model of Permanent Middle Cerebral Artery Occlusion in Transgenic Mice , 1999, Journal of neurochemistry.

[123]  P. Ponka,et al.  Cellular iron metabolism. , 1999, Kidney international. Supplement.

[124]  G. Mann,et al.  Heme oxygenase-carbon monoxide signalling pathway in atherosclerosis: anti-atherogenic actions of bilirubin and carbon monoxide? , 1999, Cardiovascular research.

[125]  M. Sayegh,et al.  In vitro and in vivo immunomodulatory effects of RDP1258, a novel synthetic peptide. , 1999, Journal of the American Society of Nephrology : JASN.

[126]  R. A. Johnson,et al.  Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions. , 1999, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[127]  P. Ponka Cell biology of heme. , 1999, The American journal of the medical sciences.

[128]  Y. Niida,et al.  Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. , 1999, The Journal of clinical investigation.

[129]  R. Tyrrell Redox regulation and oxidant activation of heme oxygenase-1. , 1999, Free radical research.

[130]  K. Takahashi,et al.  Suppression of heme oxygenase-1 mRNA expression by interferon-gamma in human glioblastoma cells. , 1999, Journal of neurochemistry.

[131]  J. Platt,et al.  Heme oxygenase: Protective gene or Trojan horse , 1998, Nature Medicine.

[132]  L. Turka,et al.  Antibody-induced transplant arteriosclerosis is prevented by graft expression of anti-oxidant and anti-apoptotic genes , 1998, Nature Medicine.

[133]  S. Numazawa,et al.  The expression of heme oxygenase-1 gene responded to oxidative stress produced by phorone, a glutathione depletor, in the rat liver; the relevance to activation of c-jun n-terminal kinase. , 1998, The Journal of pharmacology and experimental therapeutics.

[134]  R. Colvin,et al.  Expression of heme oxygenase-1 can determine cardiac xenograft survival , 1998, Nature Medicine.

[135]  W. Durante,et al.  Carbon monoxide and vascular cell function (review). , 1998, International journal of molecular medicine.

[136]  A. Alayash,et al.  Acellular hemoglobin-mediated oxidative stress toward endothelium: a role for ferryl iron. , 1998, American journal of physiology. Heart and circulatory physiology.

[137]  Arun J Sharma,et al.  Induction of Heme Oxygenase-1 During Endotoxemia Is Downregulated by Transforming Growth Factor-β1 , 1998 .

[138]  P. Barnes,et al.  Raised levels of exhaled carbon monoxide are associated with an increased expression of heme oxygenase-1 in airway macrophages in asthma: a new marker of oxidative stress , 1998, Thorax.

[139]  P. Kaminski,et al.  Oxidant--nitric oxide signalling mechanisms in vascular tissue. , 1998, Biochemistry. Biokhimiia.

[140]  L. Noble,et al.  Induction of heme oxygenase-1 (HO-1) in the contused spinal cord of the rat , 1998, Brain Research.

[141]  H. Bonkovsky,et al.  Mechanism of Sodium Arsenite-mediated Induction of Heme Oxygenase-1 in Hepatoma Cells , 1998, The Journal of Biological Chemistry.

[142]  S. Fuggle,et al.  Cell adhesion molecules in clinical renal transplantation. , 1998, Transplantation.

[143]  V. Cattell,et al.  Heme oxygenase is induced in nephrotoxic nephritis and hemin, a stimulator of heme oxygenase synthesis, ameliorates disease. , 1998, Kidney international.

[144]  R. Cotran,et al.  Endothelial adhesion molecules in health and disease. , 1998, Pathologie-biologie.

[145]  T. Kietzmann,et al.  The rat heme oxygenase-1 gene is transcriptionally induced via the protein kinase A signaling pathway in rat hepatocyte cultures. , 1998, Molecular pharmacology.

[146]  J. Megyesi,et al.  Induction of p21WAF1/CIP1/SDI1 in kidney tubule cells affects the course of cisplatin-induced acute renal failure. , 1998, The Journal of clinical investigation.

[147]  J. Grande,et al.  Intracellular targets in heme protein-induced renal injury. , 1998, Kidney international.

[148]  N. Abraham,et al.  Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis , 1998, Journal of cellular biochemistry.

[149]  S. yet,et al.  Induction of heme oxygenase-1 during endotoxemia is downregulated by transforming growth factor-beta1. , 1998, Circulation research.

[150]  S. Tonegawa,et al.  Ejaculatory abnormalities in mice with targeted disruption of the gene for heme oxygenase-2 , 1998, Nature Medicine.

[151]  N. Abraham,et al.  Heme Induces the Expression of Adhesion Molecules ICAM-1, VCAM-1, and E Selectin in Vascular Endothelial Cells , 1997, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[152]  R. Hebbel Adhesive interactions of sickle erythrocytes with endothelium. , 1997, The Journal of clinical investigation.

[153]  S. Tonegawa,et al.  Reduced stress defense in heme oxygenase 1-deficient cells. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[154]  S. Tonegawa,et al.  Heme oxygenase 1 is required for mammalian iron reutilization. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[155]  R. D. De Lisle,et al.  Expression of oxidative stress-responsive genes and cytokine genes during caerulein-induced acute pancreatitis. , 1997, The American journal of physiology.

[156]  C. T. Wagner,et al.  Hemodynamic forces induce the expression of heme oxygenase in cultured vascular smooth muscle cells. , 1997, The Journal of clinical investigation.

[157]  D. Willoughby,et al.  COX-2, HO NO! Cyclooxygenase-2, heme oxygenase and nitric oxide synthase: Their role and interactions in inflammation. BIRAs Symposium, Saint Bartholomew's Hospital, London, 26 April 1996 , 1997, Inflammation Research.

[158]  J. D. Engel,et al.  The world according to Maf. , 1997, Nucleic acids research.

[159]  M. Maines,et al.  Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. , 1997, European journal of biochemistry.

[160]  A. Adeagbo Endothelium-derived hyperpolarizing factor: characterization as a cytochrome P450 1A-linked metabolite of arachidonic acid in perfused rat mesenteric prearteriolar bed. , 1997, American journal of hypertension.

[161]  D. Ferriero,et al.  Hypoxia-Ischemia, but Not Hypoxia Alone, Induces the Expression of Heme Oxygenase-1 (HSP32) in Newborn Rat Brain , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[162]  N. Abraham,et al.  Heme oxygenase induction with attenuation of experimentally induced corneal inflammation. , 1997, Biochemical pharmacology.

[163]  K. Griendling,et al.  Heme oxygenase-1 is regulated by angiotensin II in rat vascular smooth muscle cells. , 1997, Hypertension.

[164]  U. Muller-eberhard,et al.  Gene regulation of HBP 23 by metalloporphyrins and protoporphyrin IX in liver and hepatocyte cultures. , 1997, Biochemical and biophysical research communications.

[165]  H. Fessler,et al.  Mechanism of hemoglobin-induced protection against endotoxemia in rats: a ferritin-independent pathway. , 1997, The American journal of physiology.

[166]  M. Maines,et al.  The heme oxygenase system: a regulator of second messenger gases. , 1997, Annual review of pharmacology and toxicology.

[167]  G. Gourley Bilirubin metabolism and kernicterus. , 1997, Advances in pediatrics.

[168]  G. Shires,et al.  Expression of adhesion molecules and von Willebrand factor in human coronary artery endothelial cells incubated with differently modified hemoglobin solutions. , 1997, Artificial cells, blood substitutes, and immobilization biotechnology.

[169]  J. Alam,et al.  Glomerular inflammation induces resistance to tubular injury in the rat. A novel form of acquired, heme oxygenase-dependent resistance to renal injury. , 1996, The Journal of clinical investigation.

[170]  J. Delanghe,et al.  Biological and clinical significance of haptoglobin polymorphism in humans. , 1996, Clinical chemistry.

[171]  A. Choi,et al.  Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[172]  M. Goligorsky,et al.  Dual role of heme oxygenase in epithelial cell injury: contrasting effects of short-term and long-term exposure to oxidant stress. , 1996, The Journal of laboratory and clinical medicine.

[173]  T. Shono,et al.  Involvement of the transcription factor NF-kappaB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress , 1996, Molecular and cellular biology.

[174]  F. Luft,et al.  Antisense oligonucleotides for ICAM-1 attenuate reperfusion injury and renal failure in the rat. , 1996, Kidney international.

[175]  K. Kinzler,et al.  Genetic determinants of p53-induced apoptosis and growth arrest. , 1996, Genes & development.

[176]  P. Harrison,et al.  The ferritins: molecular properties, iron storage function and cellular regulation. , 1996, Biochimica et biophysica acta.

[177]  A. Choi,et al.  Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. , 1996, American journal of respiratory cell and molecular biology.

[178]  Ignarro Lj Physiology and pathophysiology of nitric oxide. , 1996 .

[179]  A. Choi,et al.  Regulation of heme oxygenase-1 expression in vivo and in vitro in hyperoxic lung injury. , 1996, American journal of respiratory cell and molecular biology.

[180]  M. Maines,et al.  Expression of heme oxygenase-1 (HSP32) in human prostate: normal, hyperplastic, and tumor tissue distribution. , 1996, Urology.

[181]  R. Sorensen,et al.  New concepts in the immunology of sickle cell disease. , 1996, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[182]  M. Menger,et al.  Adhesion molecules as determinants of disease: From molecular biology to surgical research , 1996, The British journal of surgery.

[183]  E. Conner,et al.  Inflammation, free radicals, and antioxidants. , 1996, Nutrition.

[184]  T. Nagai,et al.  The role of heme in gene expression. , 1996, International journal of hematology.

[185]  R. Zager Mitochondrial free radical production induces lipid peroxidation during myohemoglobinuria. , 1996, Kidney international.

[186]  S. Hunt,et al.  Higher serum bilirubin is associated with decreased risk for early familial coronary artery disease. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[187]  N. Abraham,et al.  The Biological Significance and Physiological Role of Heme Oxygenase , 1996 .

[188]  L. Ignarro Physiology and pathophysiology of nitric oxide. , 1996, Kidney international. Supplement.

[189]  D. Willis,et al.  Heme oxygenase: A novel target for the modulation of inflammatory response , 1996, Nature Medicine.

[190]  S. Kourembanas,et al.  Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide. , 1995, The Journal of clinical investigation.

[191]  A. Choi,et al.  Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase-1. , 1995, American journal of respiratory cell and molecular biology.

[192]  U. Muller-eberhard,et al.  Expression of the mRNA of heme-binding protein 23 is coordinated with that of heme oxygenase-1 by heme and heavy metals in primary rat hepatocytes and hepatoma cells. , 1995, Biochemistry.

[193]  N. Abraham,et al.  Adenovirus-mediated heme oxygenase-1 gene transfer into rabbit ocular tissues. , 1995, Investigative ophthalmology & visual science.

[194]  D. Willis,et al.  Modulation of heme oxygenase activity in rat brain and spleen by inhibitors and donors of nitric oxide. , 1995, Biochemical and biophysical research communications.

[195]  M. Gerritsen,et al.  Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[196]  S. Srivastava,et al.  Regulation of Heme Oxygenase Messenger-RNA in Mesangial Cells - Prostaglandin E2, Negatively Modulates Interleukin-1-Induced Heme Oxygenase-1 Messenger-RNA , 1995 .

[197]  P. Libby,et al.  Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. , 1995, The Journal of clinical investigation.

[198]  A. Choi,et al.  Identification of a Second Region Upstream of the Mouse Heme Oxygenase-1 Gene That Functions as a Basal Level and Inducer-dependent Transcription Enhancer (*) , 1995, The Journal of Biological Chemistry.

[199]  C. Henschke,et al.  Direct comparison of Sn-mesoporphyrin, an inhibitor of bilirubin production, and phototherapy in controlling hyperbilirubinemia in term and near-term newborns. , 1995, Pediatrics.

[200]  R. A. Johnson,et al.  A heme oxygenase product, presumably carbon monoxide, mediates a vasodepressor function in rats. , 1995, Hypertension.

[201]  G. Vercellotti,et al.  Heme protein-mediated renal injury: a protective role for 21-aminosteroids in vitro and in vivo. , 1995, Kidney international.

[202]  L. Guarente,et al.  Heme binds to a short sequence that serves a regulatory function in diverse proteins. , 1995, The EMBO journal.

[203]  S. Srivastava,et al.  Regulation of heme oxygenase mRNA in mesangial cells: prostaglandin E2 negatively modulates interleukin-1-induced heme oxygenase-1 mRNA. , 1995, Biochemical and biophysical research communications.

[204]  G S Marks,et al.  Heme oxygenase: the physiological role of one of its metabolites, carbon monoxide and interactions with zinc protoporphyrin, cobalt protoporphyrin and other metalloporphyrins. , 1994, Cellular and molecular biology.

[205]  C. Rice-Evans,et al.  Bilirubin and ascorbate antioxidant activity in neonatal plasma , 1994, FEBS letters.

[206]  G. Perry,et al.  Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease. , 1994, The American journal of pathology.

[207]  N. Abraham,et al.  Identification of binding sites for transcription factors NF-kappa B and AP-2 in the promoter region of the human heme oxygenase 1 gene. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[208]  H. Jacob Newly recognized causes of atherosclerosis: the role of microorganisms and of vascular iron overload. , 1994, The Journal of laboratory and clinical medicine.

[209]  R. Tyrrell,et al.  Heme oxygenase 1 mediates an adaptive response to oxidative stress in human skin fibroblasts. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[210]  S. Shibahara Heme oxygenase—regulation of and physiological implication in heme catabolism , 1994 .

[211]  I. London,et al.  Regulation of heme-regulated eIF-2α kinase and its expression in erythroid cells , 1994 .

[212]  M. Moore Characterization of the enzyme , 1994 .

[213]  J. Eaton,et al.  Heme and the vasculature: an oxidative hazard that induces antioxidant defenses in the endothelium. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

[214]  I. London,et al.  Regulation of heme-regulated eIF-2 alpha kinase and its expression in erythroid cells. , 1994, Biochimie.

[215]  J. Eaton,et al.  Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[216]  K. Stenzel,et al.  Immune stimulatory and anti‐tumour properties of haemin , 1993, Clinical and experimental immunology.

[217]  R. Haworth,et al.  Hemin: levels in experimental subarachnoid hematoma and effects on dissociated vascular smooth-muscle cells. , 1993, Journal of neurosurgery.

[218]  S. Shibahara,et al.  Elevated levels of heme oxygenase‐1 activity and mRNA in peripheral blood adherent cells of acquired immunodeficiency syndrome patients , 1993, American journal of hematology/oncology.

[219]  G. Drummond,et al.  Prolonged clinical use of a heme oxygenase inhibitor: hematological evidence for an inducible but reversible iron-deficiency state. , 1993, Pediatrics.

[220]  M. Timko,et al.  Regulation by heme of mitochondrial protein transport through a conserved amino acid motif. , 1993, Science.

[221]  U. Muller-eberhard,et al.  Bioactivity of heme and its containment , 1993, American journal of hematology.

[222]  M P Bevilacqua,et al.  Endothelial-leukocyte adhesion molecules. , 1993, Annual review of immunology.

[223]  R. Mayer,et al.  Induction of kidney heme oxygenase-1 (HSP32) mRNA and protein by ischemia/reperfusion: possible role of heme as both promotor of tissue damage and regulator of HSP32. , 1993, The Journal of pharmacology and experimental therapeutics.

[224]  R. Chandra,et al.  Chemistry and biology of heme. Effect of metal salts, organometals, and metalloporphyrins on heme synthesis and catabolism, with special reference to clinical implications and interactions with cytochrome P-450. , 1993, Drug metabolism reviews.

[225]  G. Vercellotti,et al.  Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. , 1992, The Journal of clinical investigation.

[226]  M. Maines Heme Oxygenase: Clinical Applications and Functions , 1992 .

[227]  M. Maines,et al.  Differential regulation of heme oxygenase isozymes by Sn- and Zn-protoporphyrins: possible relevance to suppression of hyperbilirubinemia. , 1992, Biochimica et biophysica acta.

[228]  A. Ichikawa,et al.  Induction of heme oxygenase by Δ12-prostaglandin J2 in porcine aortic endothelial cells , 1992 .

[229]  R. Tyrrell,et al.  Endogenous glutathione levels modulate both constitutive and UVA radiation/hydrogen peroxide inducible expression of the human heme oxygenase gene. , 1992, Carcinogenesis.

[230]  A. Ichikawa,et al.  Induction of heme oxygenase by delta 12-prostaglandin J2 in porcine aortic endothelial cells. , 1992, Prostaglandins.

[231]  P. Ghezzi,et al.  Interleukin-1 and tumour necrosis factor induce hepatic haem oxygenase. Feedback regulation by glucocorticoids. , 1991, The Biochemical journal.

[232]  J. Eaton,et al.  Hemin: a possible physiological mediator of low density lipoprotein oxidation and endothelial injury. , 1991, Arteriosclerosis and thrombosis : a journal of vascular biology.

[233]  N. Abraham Molecular regulation--biological role of heme in hematopoiesis. , 1991, Blood reviews.

[234]  H. Munro,et al.  Regulation of ferritin and heme oxygenase synthesis in rat fibroblasts by different forms of iron. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[235]  R. Tyrrell,et al.  Induction of heme oxygenase: a general response to oxidant stress in cultured mammalian cells. , 1991, Cancer research.

[236]  K Nakatsu,et al.  Does carbon monoxide have a physiological function? , 1991, Trends in pharmacological sciences.

[237]  L. Guarente,et al.  Functional dissection and sequence of yeast HAP1 activator , 1989, Cell.

[238]  D. Shemin An illustration of the use of isotopes: the biosynthesis of porphyrins. , 1989, BioEssays : news and reviews in molecular, cellular and developmental biology.

[239]  R. Tyrrell,et al.  Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[240]  U. Muller-eberhard,et al.  Pathophysiology of heme synthesis. , 1988, Seminars in hematology.

[241]  E. Juvonen,et al.  Erythroid colony formation and effect of hemin in vitro in hereditary sideroblastic anemias. , 1988, Experimental hematology.

[242]  J. Dawson,et al.  Probing structure-function relations in heme-containing oxygenases and peroxidases. , 1988, Science.

[243]  S. Shibahara,et al.  The physiological significance of heme oxygenase. , 1988, The International journal of biochemistry.

[244]  S. Knuutila,et al.  Heme arginate treatment for myelodysplastic syndromes. , 1988, Leukemia research.

[245]  B. Brüne,et al.  Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. , 1987, Molecular pharmacology.

[246]  S. Shibahara,et al.  Transcriptional control of rat heme oxygenase by heat shock. , 1987, The Journal of biological chemistry.

[247]  S. Numazawa,et al.  Effects of phorone (diisopropylidene acetone), a glutathione (GSH) depletor, on hepatic enzymes involved in drug and heme metabolism in rats: evidence that phorone is a potent inducer of heme oxygenase. , 1987, Biochemical and biophysical research communications.

[248]  L. Guarente,et al.  Yeast HAP1 activator competes with the factor RC2 for binding to the upstream activation site UAS1 of the CYC1 gene , 1987, Cell.

[249]  B. Ames,et al.  Bilirubin is an antioxidant of possible physiological importance. , 1987, Science.

[250]  G. Drummond,et al.  Control of heme metabolism with synthetic metalloporphyrins. , 1986, The Journal of clinical investigation.

[251]  M. Maines,et al.  Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. , 1986, The Journal of biological chemistry.

[252]  D. Lightner,et al.  'Like a shrivelled blood orange'--bilirubin, jaundice, and phototherapy. , 1985, Pediatrics.

[253]  S. Sassa,et al.  Growth‐promoting effects of iron‐ and cobalt‐protoporphyrins on cultured embryonic cells , 1983, Journal of cellular physiology.

[254]  R. Levere,et al.  Heme metabolism in erythroid and hepatic cells. , 1983, Progress in hematology.

[255]  N. Hayashi,et al.  Evidence for the transcriptional inhibition by heme of the synthesis of delta-aminolevulinate synthase in rat liver. , 1982, Biochemical and biophysical research communications.

[256]  I. London,et al.  Hemin enhances the differentiation of mouse 3T3 cells to adipocytes , 1981, Cell.

[257]  D. Gemsa MICROSOMAL HEME OXYGENASE , 1981 .

[258]  S. Sassa,et al.  The potent heme oxygenase inducing action of arsenic and parasiticidal arsenicals. , 1981, Pharmacology.

[259]  R. Hoffman,et al.  Embryonic-fetal erythroid characteristics of a human leukemic cell line. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[260]  P. Harrison,et al.  Globin synthesis and erythroid differentiation in a Friend cell variant deficient in heme synthesis. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[261]  S. Sassa,et al.  Hemin control of heme biosynthesis in mouse Friend virus-transformed erythroleukemia cells in culture. , 1978, The Journal of biological chemistry.

[262]  D. Ishii,et al.  Haemin promotes rapid neurite outgrowth in cultured mouse neuroblastoma cells , 1978, Nature.

[263]  Levere Rd,et al.  Enzymatic formation and cellular regulation of heme synthesis. , 1977 .

[264]  R. Levere,et al.  Enzymatic formation and cellular regulation of heme synthesis. , 1977, Seminars in hematology.

[265]  P. Marks,et al.  Translation and stability of human globin mRNA in Xenopus oocytes. , 1976, The Journal of clinical investigation.

[266]  T. Blaschke,et al.  A new approach to quantitation of the various sources of bilrubin in man. , 1976, The Journal of laboratory and clinical medicine.

[267]  S. Sassa,et al.  Sequential induction of heme pathway enzymes during erythroid differentiation of mouse Friend leukemia virus-infected cells , 1976, The Journal of experimental medicine.

[268]  A. Kappas,et al.  Cobalt stimulation of heme degradation in the liver. Dissociation of microsomal oxidation of heme from cytochrome P-450. , 1975, The Journal of biological chemistry.

[269]  G. Kikuchi,et al.  Sequence of the reaction of heme catabolism catalyzed by the microsomal heme oxygenase system , 1974, FEBS letters.

[270]  M. Maines,et al.  Cobalt induction of hepatic heme oxygenase; with evidence that cytochrome P-450 is not essential for this enzyme activity. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[271]  D. Gemsa,et al.  Stimulation of heme oxygenase in macrophages and liver by endotoxin. , 1974, The Journal of clinical investigation.

[272]  T. Tephly,et al.  Effect of drugs on heme synthesis in the liver. , 1971, Metabolism: clinical and experimental.

[273]  H. Marver,et al.  The enzymatic catabolism of hemoglobin: stimulation of microsomal heme oxygenase by hemin. , 1970, The Journal of laboratory and clinical medicine.

[274]  H. Marver,et al.  Microsomal heme oxygenase. Characterization of the enzyme. , 1969, The Journal of biological chemistry.

[275]  U. Muller-eberhard,et al.  Plasma concentrations of hemopexin, haptoglobin and heme in patients with various hemolytic diseases. , 1968, Blood.

[276]  H. Marver,et al.  The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. , 1968, Proceedings of the National Academy of Sciences of the United States of America.

[277]  W. J. Williams,et al.  The production of carbon monoxide from hemoglobin in vivo. , 1967, The Journal of clinical investigation.

[278]  W. J. Williams,et al.  Endogenous carbon monoxide production in patients with hemolytic anemia. , 1966, The Journal of clinical investigation.

[279]  C. J. Watson Reminiscences of Hans Fischer and His Laboratory , 2015, Perspectives in biology and medicine.

[280]  J. Ostrow,et al.  The formation of bilirubin from hemoglobin in vivo. , 1962, The Journal of clinical investigation.

[281]  T. Waldmann,et al.  Life span of red blood cell. , 1959, Physiological reviews.

[282]  G. Ritzel,et al.  Über eine biologische Bedeutung der Gallenfarbstoffe. Bilirubin und Biliverdin als Antioxydantien für das Vitamin A und die essentiellen Fettsäuren , 1954 .

[283]  C. S. Russell,et al.  δ-AMINOLEVULINIC ACID, ITS ROLE IN THE BIOSYNTHESIS OF PORPHYRINS AND PURINES1 , 1953 .

[284]  J. Wittenberg,et al.  The mechanism of porphyrin formation; the role of the tricarboxylic acid cycle. , 1951, The Journal of biological chemistry.

[285]  I. London,et al.  On the origin of bile pigment in normal man. , 1950, The Journal of biological chemistry.

[286]  T. Sjöstrand Endogenous Formation of Carbon Monoxide in Man , 1949, Nature.

[287]  T. Sjöstrand Endogenous Formation of Carbon Monoxide in Man Under Normal and Pathological Conditions , 1949 .

[288]  D. Rittenberg,et al.  The life span of the human red blood cell. , 1946, The Journal of biological chemistry.