Heat shock protein 27 (HSP27): biomarker of disease and therapeutic target

Heat shock protein 27 (HSP27) is a multidimensional protein which acts as a protein chaperone and an antioxidant and plays a role in the inhibition of apoptosis and actin cytoskeletal remodeling. In each of these capacities, HSP27 has been implicated in different disease states playing both protective and counter-protective roles. The current review presents HSP27 in multiple disease contexts: renal injury and fibrosis, cancer, neuro-degenerative and cardiovascular disease, highlighting its role as a potential biomarker and therapeutic target.

[1]  B. Thornhill,et al.  Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy. , 2009, Kidney international.

[2]  Daohai Zhang,et al.  Phosphorylation of Ser78 of Hsp27 correlated with HER-2/neu status and lymph node positivity in breast cancer , 2007, Molecular Cancer.

[3]  M. Welsh,et al.  Ischemic acute renal failure induces differential expression of small heat shock proteins. , 2000, Journal of the American Society of Nephrology : JASN.

[4]  T. Caputo,et al.  IgA antibodies to the 27‐kDa heat‐shock protein in the genital tracts of women with gynecologic cancers , 2000, International journal of cancer.

[5]  A Tissières,et al.  Heat shock of Drosophila melanogaster induces the synthesis of new messenger RNAs and proteins. , 1978, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[6]  M. Gaestel,et al.  Small heat shock proteins are molecular chaperones. , 1993, The Journal of biological chemistry.

[7]  S. Fain,et al.  Serum HSP27 is associated with medullary perfusion in kidney allografts. , 2012, Journal of nephrology.

[8]  Feng Zhang,et al.  Hsp27 Protects against Ischemic Brain Injury via Attenuation of a Novel Stress-Response Cascade Upstream of Mitochondrial Cell Death Signaling , 2008, The Journal of Neuroscience.

[9]  K. Kang,et al.  Upregulated HSP27 in human breast cancer cells reduces Herceptin susceptibility by increasing Her2 protein stability , 2008, BMC Cancer.

[10]  H. McBride,et al.  The interaction and cellular localization of HSP27 and ERbeta are modulated by 17beta-estradiol and HSP27 phosphorylation. , 2007, Molecular and cellular endocrinology.

[11]  P. Williams,et al.  Anti-heat shock protein-27 (Hsp-27) antibody levels in patients with chest pain: association with established cardiovascular risk factors. , 2008, Clinica chimica acta; international journal of clinical chemistry.

[12]  M. Nangaku Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. , 2004, Internal medicine.

[13]  A. Melcher,et al.  A simple method to cure established tumors by inflammatory killing of normal cells , 2004, Nature Biotechnology.

[14]  Y. Itoyama,et al.  Immunohistochemical localization of the low molecular weight stress protein HSP27 following focal cerebral ischemia in the rat , 1995, Brain Research.

[15]  Y. Hirose,et al.  Phosphorylation status of heat shock protein 27 plays a key role in gemcitabine-induced apoptosis of pancreatic cancer cells. , 2011, Cancer letters.

[16]  Sung-Hou Kim,et al.  Crystal structure of a small heat-shock protein , 1998, Nature.

[17]  R. Chevalier,et al.  Obstructive nephropathy: towards biomarker discovery and gene therapy , 2006, Nature Clinical Practice Nephrology.

[18]  S. Reese,et al.  HSP27 is involved in the pathogenesis of kidney tubulointerstitial fibrosis. , 2008, American journal of physiology. Renal physiology.

[19]  R. Langer,et al.  Protein Expression Profiling in Esophageal Adenocarcinoma Patients Indicates Association of Heat-Shock Protein 27 Expression and Chemotherapy Response , 2008, Clinical Cancer Research.

[20]  J. Behlke,et al.  Phosphorylation and supramolecular organization of murine small heat shock protein HSP25 abolish its actin polymerization-inhibiting activity. , 1994, The Journal of biological chemistry.

[21]  J. Landry,et al.  Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27 , 1995, Molecular and cellular biology.

[22]  Stuart K. Calderwood,et al.  Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications , 2005, Cell stress & chaperones.

[23]  G. Wick The heat is on: heat-shock proteins and atherosclerosis. , 2006, Circulation.

[24]  M. Pinzani,et al.  Fibrogenesis & Tissue Repair , 2009 .

[25]  Johannes Buchner,et al.  Regulation of Hsp27 Oligomerization, Chaperone Function, and Protective Activity against Oxidative Stress/Tumor Necrosis Factor α by Phosphorylation* , 1999, The Journal of Biological Chemistry.

[26]  J. Ingelfinger,et al.  Regulation and Localization of HSP70 and HSP25 in the Kidney of Rats Undergoing Long-Term Administration of Angiotensin II , 2002, Hypertension.

[27]  L. Rodella,et al.  Cyclosporine A induces vascular fibrosis and heat shock protein expression in rat. , 2005, International immunopharmacology.

[28]  J. Michel,et al.  Identification by a Differential Proteomic Approach of Heat Shock Protein 27 as a Potential Marker of Atherosclerosis , 2004, Circulation.

[29]  A. Cybulsky,et al.  Stress proteins in glomerular epithelial cell injury. , 2005, Contributions to nephrology.

[30]  J. Rogers,et al.  Phosphorylation Dynamics Regulate Hsp27-Mediated Rescue of Neuronal Plasticity Deficits in Tau Transgenic Mice , 2010, The Journal of Neuroscience.

[31]  V. Erdmann,et al.  Identification of the phosphorylation sites of the murine small heat shock protein hsp25. , 1991, The Journal of biological chemistry.

[32]  S. Reese,et al.  Heat Shock Protein 27 in Chronic Allograft Nephropathy: A Local Stress Response , 2005, Transplantation.

[33]  D. Ciocca,et al.  Heat shock proteins HSP27 and HSP70 in unilateral obstructed kidneys , 2003, Pediatric Nephrology.

[34]  J. Ingelfinger,et al.  Heme oxygenase-1 is upregulated in the kidney of angiotensin II-induced hypertensive rats : possible role in renoprotection. , 2000, Hypertension.

[35]  K. Herkner,et al.  HSP-25 and HSP-90 stabilize Na,K-ATPase in cytoskeletal fractions of ischemic rat renal cortex. , 2002, Kidney international.

[36]  G. Ferns,et al.  The potential role of heat shock protein 27 in cardiovascular disease. , 2012, Clinica chimica acta; international journal of clinical chemistry.

[37]  J. Landry,et al.  HSP27 phosphorylation-mediated resistance against actin fragmentation and cell death induced by oxidative stress. , 1996, Cancer research.

[38]  P. Devarajan,et al.  Renal Cell Injury: Metabolic and Structural Alterations , 1994, Pediatric Research.

[39]  J. Klein,et al.  Heat Shock Protein 27 Controls Apoptosis by Regulating Akt Activation* , 2003, Journal of Biological Chemistry.

[40]  J. Landry,et al.  Regulation of actin filament dynamics by p38 map kinase-mediated phosphorylation of heat shock protein 27. , 1997, Journal of cell science.

[41]  Guido Kroemer,et al.  Hsp27 negatively regulates cell death by interacting with cytochrome c , 2000, Nature Cell Biology.

[42]  V. D’Agati,et al.  Selective renal overexpression of human heat shock protein 27 reduces renal ischemia-reperfusion injury in mice. , 2010, American journal of physiology. Renal physiology.

[43]  Zhiyong Wang,et al.  Hsp27 Inhibits Bax Activation and Apoptosis via a Phosphatidylinositol 3-Kinase-dependent Mechanism* , 2008, Journal of Biological Chemistry.

[44]  H. McBride,et al.  The interaction and cellular localization of HSP27 and ERβ are modulated by 17β-estradiol and HSP27 phosphorylation , 2007, Molecular and Cellular Endocrinology.

[45]  M. Akbar,et al.  The Neuroprotective Effects of Heat Shock Protein 27 Overexpression in Transgenic Animals against Kainate-induced Seizures and Hippocampal Cell Death* , 2003, Journal of Biological Chemistry.

[46]  H. Grabsch,et al.  Low molecular weight heat shock protein HSP27 is a prognostic indicator in rectal cancer but not colon cancer , 2010, Gut.

[47]  Jody L. Martin,et al.  Overexpression of Wild-Type Heat Shock Protein 27 and a Nonphosphorylatable Heat Shock Protein 27 Mutant Protects Against Ischemia/Reperfusion Injury in a Transgenic Mouse Model , 2004, Circulation.

[48]  L. Rodella,et al.  Small Heat Shock Proteins Expression in Rat Kidneys Treated with Cyclosporine A Alone and Combined with Melatonin , 2002, The Histochemical Journal.

[49]  M. Gleave,et al.  OGX-427 inhibits tumor progression and enhances gemcitabine chemotherapy in pancreatic cancer , 2011, Cell Death and Disease.

[50]  P. Mehlen,et al.  Large unphosphorylated aggregates as the active form of hsp27 which controls intracellular reactive oxygen species and glutathione levels and generates a protection against TNFalpha in NIH-3T3-ras cells. , 1997, Biochemical and biophysical research communications.

[51]  S. Chaufour,et al.  Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels. , 2005, Antioxidants & redox signaling.

[52]  S. Chiou,et al.  Chemoresistance of lung cancer stemlike cells depends on activation of Hsp27 , 2011, Cancer.

[53]  Sean B Fain,et al.  BOLD-MRI assessment of intrarenal oxygenation and oxidative stress in patients with chronic kidney allograft dysfunction. , 2007, American journal of physiology. Renal physiology.

[54]  S. Charette,et al.  The Interaction of HSP27 with Daxx Identifies a Potential Regulatory Role of HSP27 in Fas‐Induced Apoptosis , 2000, Annals of the New York Academy of Sciences.

[55]  C. Anderson,et al.  Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II. , 1992, The Journal of biological chemistry.

[56]  E. Neilson,et al.  Mechanisms of tubulointerstitial fibrosis. , 2010, Journal of the American Society of Nephrology : JASN.

[57]  A. Mauk,et al.  Self-association and Chaperone Activity of Hsp27 Are Thermally Activated* , 2006, Journal of Biological Chemistry.

[58]  J. Belleroche,et al.  Mice that overexpress human heat shock protein 27 have increased renal injury following ischemia reperfusion. , 2009, Kidney international.

[59]  S. Hilsenbeck,et al.  Hsp27 overexpression inhibits doxorubicin–induced apoptosis in human breast cancer cells , 1999, Breast Cancer Research and Treatment.

[60]  D. Sawyer,et al.  Heat shock proteins in cancer: chaperones of tumorigenesis. , 2006, Trends in biochemical sciences.