Role of Forkhead Transcription Factors in Diabetes-Induced Oxidative Stress

Diabetes is a chronic metabolic disorder, characterized by hyperglycemia resulting from insulin deficiency and/or insulin resistance. Recent evidence suggests that high levels of reactive oxygen species (ROS) and subsequent oxidative stress are key contributors in the development of diabetic complications. The FOXO family of forkhead transcription factors including FOXO1, FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular and biological processes and are critical regulators of cellular oxidative stress response pathways. FOXO1 transcription factors can affect a number of different tissues including liver, retina, bone, and cell types ranging from hepatocytes to microvascular endothelial cells and pericytes to osteoblasts. They are induced by oxidative stress and contribute to ROS-induced cell damage and apoptosis. In this paper, we discuss the role of FOXO transcription factors in mediating oxidative stress-induced cellular response.

[1]  D. Tindall,et al.  Regulation of FOXO protein stability via ubiquitination and proteasome degradation. , 2011, Biochimica et biophysica acta.

[2]  A. Lombardi,et al.  Methylglyoxal impairs insulin signalling and insulin action on glucose-induced insulin secretion in the pancreatic beta cell line INS-1E , 2011, Diabetologia.

[3]  H. Broxmeyer,et al.  Superoxide flashes, reactive oxygen species, and the mitochondrial permeability transition pore: potential implications for hematopoietic stem cell function , 2011, Current opinion in hematology.

[4]  E. Moran,et al.  FOXO1 modulates osteoblast differentiation. , 2011, Bone.

[5]  P. Winocour,et al.  Oxidative stress in early diabetic nephropathy: fueling the fire , 2011, Nature Reviews Endocrinology.

[6]  J. Rains,et al.  Oxidative stress, insulin signaling, and diabetes. , 2011, Free radical biology & medicine.

[7]  B. Burgering,et al.  Forkhead box o as a sensor, mediator, and regulator of redox signaling. , 2011, Antioxidants & redox signaling.

[8]  Peter Storz,et al.  Forkhead homeobox type O transcription factors in the responses to oxidative stress. , 2011, Antioxidants & redox signaling.

[9]  C. Glass,et al.  FoxO1 regulates Tlr4 inflammatory pathway signalling in macrophages , 2010, The EMBO journal.

[10]  R. Xavier,et al.  Wnt signaling regulates mitochondrial physiology and insulin sensitivity. , 2010, Genes & development.

[11]  M. Diamond-Stanic,et al.  Direct inhibition by angiotensin II of insulin‐dependent glucose transport activity in mammalian skeletal muscle involves a ROS‐dependent mechanism , 2010, Archives of physiology and biochemistry.

[12]  D. Graves,et al.  FOXO1 plays an essential role in apoptosis of retinal pericytes , 2010, Molecular vision.

[13]  W. Sivitz,et al.  Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. , 2010, Antioxidants & redox signaling.

[14]  Thomas A Einhorn,et al.  TNF-α Mediates Diabetes-Enhanced Chondrocyte Apoptosis During Fracture Healing and Stimulates Chondrocyte Apoptosis Through FOXO1 , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[15]  R. DePinho,et al.  FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice. , 2010, Cell metabolism.

[16]  R. DePinho,et al.  FoxO1 is a positive regulator of bone formation by favoring protein synthesis and resistance to oxidative stress in osteoblasts. , 2010, Cell metabolism.

[17]  D. Graves,et al.  Impaired wound healing in mouse models of diabetes is mediated by TNF-α dysregulation and associated with enhanced activation of forkhead box O1 (FOXO1) , 2010, Diabetologia.

[18]  P. Puigserver,et al.  Foxo1 integrates insulin signaling with mitochondrial function in the liver , 2009, Nature Medicine.

[19]  Thomas A Einhorn,et al.  High levels of tumor necrosis factor-alpha contribute to accelerated loss of cartilage in diabetic fracture healing. , 2009, The American journal of pathology.

[20]  Yi Lu,et al.  FoxO1 Links Insulin Resistance to Proinflammatory Cytokine IL-1β Production in Macrophages , 2009, Diabetes.

[21]  N. Calcutt,et al.  Therapies for hyperglycaemia-induced diabetic complications: from animal models to clinical trials , 2009, Nature Reviews Drug Discovery.

[22]  D. Graves,et al.  FOXO1 Plays an Important Role in Enhanced Microvascular Cell Apoptosis and Microvascular Cell Loss in Type 1 and Type 2 Diabetic Rats , 2009, Diabetes.

[23]  D. Graves,et al.  Activation of the Acquired Immune Response Reduces Coupled Bone Formation in Response to a Periodontal Pathogen1 , 2008, The Journal of Immunology.

[24]  P. Witting,et al.  Redox control of endothelial function and dysfunction: molecular mechanisms and therapeutic opportunities. , 2008, Antioxidants & redox signaling.

[25]  E. Lam,et al.  Many forks in the path: cycling with FoxO , 2008, Oncogene.

[26]  P. Coffer,et al.  FOXO-binding partners: it takes two to tango , 2008, Oncogene.

[27]  E. Lam,et al.  The emerging roles of forkhead box (Fox) proteins in cancer , 2007, Nature Reviews Cancer.

[28]  R. DePinho,et al.  Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor Foxo1 in liver. , 2007, Cell metabolism.

[29]  E. Araki,et al.  Impact of mitochondrial ROS production on diabetic vascular complications. , 2007, Diabetes research and clinical practice.

[30]  B. Burgering,et al.  Stressing the role of FoxO proteins in lifespan and disease , 2007, Nature Reviews Molecular Cell Biology.

[31]  D. Graves,et al.  Advanced glycation end products induce apoptosis in fibroblasts through activation of ROS, MAP kinases, and the FOXO1 transcription factor. , 2007, American journal of physiology. Cell physiology.

[32]  Yonghong Xiao,et al.  FoxOs Are Lineage-Restricted Redundant Tumor Suppressors and Regulate Endothelial Cell Homeostasis , 2007, Cell.

[33]  S. Armstrong,et al.  FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress , 2007, Cell.

[34]  E. Araki,et al.  Impact of mitochondrial ROS production in the pathogenesis of diabetes mellitus and its complications. , 2006, Antioxidants & redox signaling.

[35]  Judit Villén,et al.  A Conserved MST-FOXO Signaling Pathway Mediates Oxidative-Stress Responses and Extends Life Span , 2006, Cell.

[36]  D. Graves,et al.  FOXO1 Functions as a Master Switch That Regulates Gene Expression Necessary for Tumor Necrosis Factor-induced Fibroblast Apoptosis* , 2005, Journal of Biological Chemistry.

[37]  D. Tindall,et al.  Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[38]  J. Bos,et al.  FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK , 2004, The EMBO journal.

[39]  R. de Caterina,et al.  Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. , 2004, Cardiovascular research.

[40]  R. Medema,et al.  FOXO4 Is Acetylated upon Peroxide Stress and Deacetylated by the Longevity Protein hSir2SIRT1* , 2004, Journal of Biological Chemistry.

[41]  Steven P. Gygi,et al.  Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase , 2004, Science.

[42]  Delin Chen,et al.  Mammalian SIRT1 Represses Forkhead Transcription Factors , 2004, Cell.

[43]  E. Lam,et al.  Cell Cycle Inhibition by FoxO Forkhead Transcription Factors Involves Downregulation of Cyclin D , 2002, Molecular and Cellular Biology.

[44]  Geert J. P. L. Kops,et al.  Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress , 2002, Nature.

[45]  N. Motoyama,et al.  FOXO Forkhead Transcription Factors Induce G2-M Checkpoint in Response to Oxidative Stress* , 2002, The Journal of Biological Chemistry.

[46]  Timothy S Kern,et al.  Activation of nuclear factor-kappaB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. , 2002, Diabetes.

[47]  D. Dowbenko,et al.  The Forkhead Transcription Factor AFX Activates Apoptosis by Induction of the BCL-6 Transcriptional Repressor* , 2002, The Journal of Biological Chemistry.

[48]  S. R. Datta,et al.  DNA Repair Pathway Stimulated by the Forkhead Transcription Factor FOXO3a Through the Gadd45 Protein , 2002, Science.

[49]  S. Nemoto,et al.  Redox Regulation of Forkhead Proteins Through a p66shc-Dependent Signaling Pathway , 2002, Science.

[50]  M. Loda,et al.  Forkhead Transcription Factors Are Critical Effectors of Cell Death and Cell Cycle Arrest Downstream of PTEN , 2000, Molecular and Cellular Biology.

[51]  R. Medema,et al.  AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1 , 2000, Nature.

[52]  L. Ignarro,et al.  Inhibitors of the proteasome pathway interfere with induction of nitric oxide synthase in macrophages by blocking activation of transcription factor NF-kappa B. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[53]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[54]  W. Garvey,et al.  New insights into the metabolic regulation of insulin action and insulin resistance: role of glucose and amino acids , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[55]  D. Godin,et al.  Alterations in Free Radical Tissue-Defense Mechanisms in Streptozocin-Induced Diabetes in Rat: Effects of Insulin Treatment , 1987, Diabetes.

[56]  Dhiren P. Shah,et al.  ON OXIDATIVE STRESS AND DIABETIC COMPLICATIONS , 2013 .

[57]  F. Zaccardi,et al.  Oxidative stress, nitric oxide, and diabetes. , 2010, The review of diabetic studies : RDS.