From endoplasmic-reticulum stress to the inflammatory response

The endoplasmic reticulum is responsible for much of a cell's protein synthesis and folding, but it also has an important role in sensing cellular stress. Recently, it has been shown that the endoplasmic reticulum mediates a specific set of intracellular signalling pathways in response to the accumulation of unfolded or misfolded proteins, and these pathways are collectively known as the unfolded-protein response. New observations suggest that the unfolded-protein response can initiate inflammation, and the coupling of these responses in specialized cells and tissues is now thought to be fundamental in the pathogenesis of inflammatory diseases. The knowledge gained from this emerging field will aid in the development of therapies for modulating cellular stress and inflammation.

[1]  D. Ron,et al.  Interferon-γ inhibits central nervous system remyelination through a process modulated by endoplasmic reticulum stress , 2006 .

[2]  Hiderou Yoshida,et al.  Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1. , 2007, Developmental cell.

[3]  G. Hotamisligil,et al.  Inflammation and metabolic disorders , 2006, Nature.

[4]  M. DeLegge,et al.  Neurodegeneration and Inflammation. , 2008, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

[5]  George Kuriakose,et al.  The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages , 2003, Nature Cell Biology.

[6]  D. Bredt,et al.  Nitric oxide synthase in cardiac sarcoplasmic reticulum. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  K. Williams,et al.  Atherosclerosis and Inflammation , 2002, Science.

[8]  H. Pahl,et al.  Expression of influenza virus hemagglutinin activates transcription factor NF-kappa B , 1995, Journal of virology.

[9]  M. Karin,et al.  Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[10]  E. Frohman,et al.  Multiple sclerosis--the plaque and its pathogenesis. , 2006, The New England journal of medicine.

[11]  R. Kaufman Orchestrating the unfolded protein response in health and disease. , 2002, The Journal of clinical investigation.

[12]  Aiqing He,et al.  The Unfolded Protein Response Is an Important Regulator of Inflammatory Genes in Endothelial Cells , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[13]  Peter Libby,et al.  The immune response in atherosclerosis: a double-edged sword , 2006, Nature Reviews Immunology.

[14]  A. Komar,et al.  The Zipper Model of Translational Control A Small Upstream ORF Is the Switch that Controls Structural Remodeling of an mRNA Leader , 2003, Cell.

[15]  H. Hayashi,et al.  TRB3, a novel ER stress‐inducible gene, is induced via ATF4–CHOP pathway and is involved in cell death , 2005, The EMBO journal.

[16]  D. Ron,et al.  The integrated stress response prevents demyelination by protecting oligodendrocytes against immune-mediated damage. , 2007, The Journal of clinical investigation.

[17]  F. Urano,et al.  Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. , 2000, Science.

[18]  Jing Deng,et al.  Translational Repression Mediates Activation of Nuclear Factor Kappa B by Phosphorylated Translation Initiation Factor 2 , 2004, Molecular and Cellular Biology.

[19]  Michael Karin,et al.  A central role for JNK in obesity and insulin resistance , 2002, Nature.

[20]  H. Yamaguchi,et al.  CHOP Is Involved in Endoplasmic Reticulum Stress-induced Apoptosis by Enhancing DR5 Expression in Human Carcinoma Cells* , 2004, Journal of Biological Chemistry.

[21]  R. Kaufman,et al.  Autocrine Tumor Necrosis Factor Alpha Links Endoplasmic Reticulum Stress to the Membrane Death Receptor Pathway through IRE1α-Mediated NF-κB Activation and Down-Regulation of TRAF2 Expression , 2006, Molecular and Cellular Biology.

[22]  Robert M. Silva,et al.  CHOP/GADD153 is a mediator of apoptotic death in substantia nigra dopamine neurons in an in vivo neurotoxin model of parkinsonism , 2005, Journal of neurochemistry.

[23]  R. Schwabe,et al.  Free cholesterol-loaded macrophages are an abundant source of tumor necrosis factor-alpha and interleukin-6: model of NF-kappaB- and map kinase-dependent inflammation in advanced atherosclerosis. , 2005, The Journal of biological chemistry.

[24]  Jonathan S. Weissman,et al.  Oxidative protein folding in eukaryotes: mechanisms and consequences , 2004 .

[25]  J. Alan Diehl,et al.  PERK-dependent Activation of Nrf2 Contributes to Redox Homeostasis and Cell Survival following Endoplasmic Reticulum Stress* , 2004, Journal of Biological Chemistry.

[26]  David A. Brenner,et al.  Free Cholesterol-loaded Macrophages Are an Abundant Source of Tumor Necrosis Factor-α and Interleukin-6 , 2005, Journal of Biological Chemistry.

[27]  R. Sood,et al.  Translational Control -subunit Kinase, Pek, Involved in Α Pancreatic Eukaryotic Initiation Factor 2 Identification and Characterization Of , 1998 .

[28]  Randal J. Kaufman,et al.  Endoplasmic Reticulum Stress Activates Cleavage of CREBH to Induce a Systemic Inflammatory Response , 2006, Cell.

[29]  D. Ron,et al.  Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response , 2004, The Journal of cell biology.

[30]  G. Kroemer,et al.  Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis , 2008, Oncogene.

[31]  R. Saunders,et al.  Antioxidant and cytoprotective responses to redox stress. , 2004, Biochemical Society symposium.

[32]  M. White,et al.  Phosphorylation of Ser307 in Insulin Receptor Substrate-1 Blocks Interactions with the Insulin Receptor and Inhibits Insulin Action* , 2002, The Journal of Biological Chemistry.

[33]  Anne Bertolotti,et al.  Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response , 2000, Nature Cell Biology.

[34]  Benjamin P Tu,et al.  The FAD- and O(2)-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum. , 2002, Molecular cell.

[35]  K. Mori,et al.  Tumor Necrosis Factor α (TNFα) Induces the Unfolded Protein Response (UPR) in a Reactive Oxygen Species (ROS)-dependent Fashion, and the UPR Counteracts ROS Accumulation by TNFα* , 2005, Journal of Biological Chemistry.

[36]  S. Hotop,et al.  Transient Cerebral Ischemia Activates Processing of xbp1 Messenger RNA Indicative of Endoplasmic Reticulum Stress , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[37]  Tetsuro Ito,et al.  Vaticanol B, a resveratrol tetramer, regulates endoplasmic reticulum stress and inflammation. , 2007, American journal of physiology. Cell physiology.

[38]  M. Tansey,et al.  Neuroinflammatory mechanisms in Parkinson's disease: Potential environmental triggers, pathways, and targets for early therapeutic intervention , 2007, Experimental Neurology.

[39]  Donna D. Zhang Mechanistic Studies of the Nrf2-Keap1 Signaling Pathway , 2006, Drug metabolism reviews.

[40]  R. Paules,et al.  An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. , 2003, Molecular cell.

[41]  M. Berridge,et al.  Calcium signalling: dynamics, homeostasis and remodelling , 2003, Nature reviews. Molecular cell biology.

[42]  L. Glimcher,et al.  Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes , 2004, Science.

[43]  E. Yilmaz,et al.  Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes , 2006, Science.

[44]  A. Cross,et al.  A little stress is good: IFN-gamma, demyelination, and multiple sclerosis. , 2007, The Journal of clinical investigation.

[45]  Randal J. Kaufman,et al.  Nrf2 Is a Direct PERK Substrate and Effector of PERK-Dependent Cell Survival , 2003, Molecular and Cellular Biology.

[46]  B. Robinson,et al.  Mitochondria, oxygen free radicals, disease and ageing. , 2000, Trends in biochemical sciences.

[47]  Joseph L Goldstein,et al.  Regulated Intramembrane Proteolysis A Control Mechanism Conserved from Bacteria to Humans , 2000, Cell.

[48]  D. Scheuner,et al.  Ultraviolet Light Activates NFκB through Translational Inhibition of IκBα Synthesis* , 2004, Journal of Biological Chemistry.

[49]  R. Kaufman,et al.  ATF6alpha optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. , 2007, Developmental cell.

[50]  R. Ransohoff,et al.  The many roles of chemokines and chemokine receptors in inflammation. , 2006, The New England journal of medicine.

[51]  J. Castilla,et al.  Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis , 2008, Proceedings of the National Academy of Sciences.

[52]  T. Kietzmann,et al.  The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control. , 2006, Antioxidants & redox signaling.

[53]  R. Kaufman,et al.  The mammalian unfolded protein response. , 2003, Annual review of biochemistry.

[54]  X. Chen,et al.  ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. , 2000, Molecular cell.

[55]  Junying Yuan,et al.  A Selective Inhibitor of eIF2α Dephosphorylation Protects Cells from ER Stress , 2005, Science.

[56]  J. Stamler,et al.  Biochemistry of nitric oxide and its redox-activated forms. , 1992, Science.

[57]  P. Walter,et al.  Signal integration in the endoplasmic reticulum unfolded protein response , 2007, Nature Reviews Molecular Cell Biology.

[58]  Y. Yoshioka,et al.  Involvement of Endoplasmic Reticulum Stress on the Cell Death Induced by 6-Hydroxydopamine in Human Neuroblastoma SH-SY5Y Cells , 2006, Neurochemical Research.

[59]  R. Kaufman,et al.  Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? , 2007, Antioxidants & redox signaling.

[60]  I. Charles,et al.  Nitric oxide induces coupling of mitochondrial signalling with the endoplasmic reticulum stress response , 2004, Nature Cell Biology.

[61]  C. Kaiser,et al.  Competition between glutathione and protein thiols for disulphide-bond formation , 1999, Nature Cell Biology.

[62]  Takashi Uehara,et al.  S-Nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration , 2006, Nature.

[63]  R. Kopito,et al.  Impairment of the ubiquitin-proteasome system by protein aggregation. , 2001, Science.

[64]  Peter Walter,et al.  Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase , 1993, Cell.

[65]  E. Falk,et al.  Association of Multiple Cellular Stress Pathways With Accelerated Atherosclerosis in Hyperhomocysteinemic Apolipoprotein E-Deficient Mice , 2004, Circulation.

[66]  H. Pahl,et al.  Activation of NF‐κB by ER stress requires both Ca2+ and reactive oxygen intermediates as messengers , 1996, FEBS letters.

[67]  Takanori Yokota,et al.  Als-linked Mutant Sod1 Induces Er Stress-and Ask1-dependent Motor Neuron Death by Targeting Derlin-1 -induced Cell Death Remains Controversial. Here We Show That Sod1 Mut Specifically Interacted with Derlin-1, a Component of Endoplasmic Reticulum (er)-associated Degradation (erad) Machinery and Trig , 2022 .

[68]  H. Wootz,et al.  ER stress and neurodegenerative diseases , 2006, Cell Death and Differentiation.

[69]  Tomomi Gotoh,et al.  ER Stress Triggers Apoptosis by Activating BH3-Only Protein Bim , 2007, Cell.

[70]  K. Mori,et al.  Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. , 1999, Molecular biology of the cell.

[71]  D. Ron,et al.  Perk is essential for translational regulation and cell survival during the unfolded protein response. , 2000, Molecular cell.

[72]  R. Kaufman,et al.  Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. , 1999, Genes & development.

[73]  D. Ron,et al.  Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase , 1999, Nature.

[74]  R. Davis,et al.  Signal Transduction by the JNK Group of MAP Kinases , 2000, Cell.

[75]  Katerina Akassoglou,et al.  NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α , 2008, Nature.

[76]  D. Ron,et al.  Endoplasmic reticulum stress modulates the response of myelinating oligodendrocytes to the immune cytokine interferon-γ , 2005, The Journal of cell biology.

[77]  J. Sambrook,et al.  A transmembrane protein with a cdc2+ CDC28 -related kinase activity is required for signaling from the ER to the nucleus , 1993, Cell.

[78]  W. Caselmann,et al.  Hepatitis B virus transactivator MHBst: activation of NF‐kappa B, selective inhibition by antioxidants and integral membrane localization. , 1992, The EMBO journal.

[79]  K. Kohno How transmembrane proteins sense endoplasmic reticulum stress. , 2007, Antioxidants & redox signaling.

[80]  R. Takahashi,et al.  Expanding insights on the involvement of endoplasmic reticulum stress in Parkinson's disease. , 2007, Antioxidants & redox signaling.

[81]  M. Cnop,et al.  Free Fatty Acids and Cytokines Induce Pancreatic β-Cell Apoptosis by Different Mechanisms: Role of Nuclear Factor-κB and Endoplasmic Reticulum Stress , 2004 .