Multifaceted Role of Heat Stress Proteins in the Kidney

  • Andrea Havasi
  • Jonathan M. Gall
  • Steven C. BorkanEmail author
Part of the Heat Shock Proteins book series (HESP, volume 5)


The kidney represents an ideal “laboratory” for assessing the role of physiologic stresses on stress proteins. This organ is equally well suited for assessing the protective effects of stress proteins against known renal insults. As a metabolically active organ that operates on the brink of “hypoxic disaster” and is capable of concentrating therapeutic agents to levels far higher than present in the circulation, the kidney is vulnerable to diverse stressors that include oxygen deprivation, ischemia, and nephrotoxin. Stress proteins exert potent stabilizing effects on epithelial cell architecture that represent reversible or “sublethal injury.” Stress proteins also promote cell survival, partly by interrupting the apoptotic pathway that contributes to organ failure. HSPs target different checkpoints in the cell death pathway, often utilizing distinct functional domains within a single HSPs to exert multiple cytoprotective effects. In sharp contrast to their protective effects in the intracellular milieu, recent evidence shows that HSPs in the extracellular compartment are pro-inflammatory. Given the relative paucity of treatments available to prevent injury or promote renal recovery, manipulation of endogenous stress proteins represents a promising arena for defining new approaches to nephrologic problems that contribute to substantial human morbidity and mortality


Apoptosis BCL2 hypoxia ischemia nephrotoxins osmotic stress 



A1 adenosine receptors


apoptosis inducing factor


acute kidney injury


apoptotic volume decrease


blood urea nitrogen


chronic allograft nephropathy


chronic kidney disease


epithelial to mesenchymal transformation




glycogen synthase kinase 3-beta


heat shock element


heat shock factor


heat shock protein




nitric oxide


osmotic response element

PI3 kinase

phosphatidyl inositide 3 kinase


reactive oxygen species


tonicity-responsive enhancer binding protein


urea transporter-A


  1. Abe, K., Ozono, Y., Miyazaki, M., Koji, T., Shioshita, K., Furusu, A., Tsukasaki, S., Matsuya, F., Hosokawa, N., Harada, T., Taguchi, T., Nagata, K. and Kohno, S. (2000) Interstitial expression of heat shock protein 47 and alpha-smooth muscle actin in renal allograft failure. Nephrol Dial Transplant 15, 529–35.PubMedCrossRefGoogle Scholar
  2. Agarraberes, F. A. and Dice, J. F. (2001) A molecular chaperone complex at the lysosomal membrane is required for protein translocation. J Cell Sci 114, 2491–9.PubMedGoogle Scholar
  3. Agarwal, R. (2003) Proinflammatory effects of oxidative stress in chronic kidney disease: role of additional angiotensin II blockade. Am J Physiol Renal Physiol 284, F863–9.PubMedGoogle Scholar
  4. Alevy, Y. G., Brennan, D., Durriya, S., Howard, T. and Mohanakumar, T. (1996) Increased expression of the HDJ-2 heat shock protein in biopsies of human rejected kidney. Transplantation 61, 963–7.PubMedCrossRefGoogle Scholar
  5. Alfieri, R. R., Bonelli, M. A., Petronini, P. G. and Borghetti, A. F. (2002) Stabilization of hsp70 mRNA on prolonged cell exposure to hypertonicity. Biochim Biophys Acta 1592, 135–40.PubMedGoogle Scholar
  6. Alfieri, R., Petronini, P. G., Urbani, S. and Borghetti, A. F. (1996) Activation of heat-shock transcription factor 1 by hypertonic shock in 3T3 cells. Biochem J 319 (Pt 2), 601–6.PubMedGoogle Scholar
  7. Asea, A. (2008) Heat shock proteins and toll-like receptors. Handb Exp Pharmacol 183, 111–27.PubMedGoogle Scholar
  8. Asea, A., Kraeft, S. K., Kurt-Jones, E. A., Stevenson, M. A., Chen, L. B., Finberg, R. W., Koo, G. C. and Calderwood, S. K. (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6, 435–42.PubMedGoogle Scholar
  9. Aufricht, C., Ardito, T., Thulin, G., Kashgarian, M., Siegel, N. J. and Van Why, S. K. (1998a) Heat-shock protein 25 induction and redistribution during actin reorganization after renal ischemia. Am J Physiol 274, F215–F22.PubMedGoogle Scholar
  10. Aufricht, C., Lu, E., Thulin, G., Kashgarian, M., Siegel, N. J. and Van Why, S. K. (1998b) ATP releases HSP-72 from protein aggregates after renal ischemia. Am J Physiol 274, F268–74.PubMedGoogle Scholar
  11. Baler, R., Dahl, G. and Voellmy, R. (1993) Activation of human heat shock genes is accompanied by oligomerization, modification, and rapid translocation of heat shock transcription factor HSF1. Mol Cell Biol 13, 2486–96.PubMedGoogle Scholar
  12. Basile, D. P., Donohoe, D., Cao, X. and Van Why, S. K. (2004) Resistance to ischemic acute renal failure in the Brown Norway rat: a new model to study cytoprotection. Kidney Int 65, 2201–11.PubMedCrossRefGoogle Scholar
  13. Bausero, M. A., Gastpar, R., Multhoff, G. and Asea, A. (2005) Alternative mechanism by which IFN-gamma enhances tumor recognition: active release of heat shock protein 72. J Immunol 175, 2900–12.PubMedGoogle Scholar
  14. Beck, F. X., Grunbein, R., Lugmayr, K. and Neuhofer, W. (2000) Heat shock proteins and the cellular response to osmotic stress. Cell Physiol Biochem 10, 303–6.PubMedCrossRefGoogle Scholar
  15. Beere, H. M., Wolf, B. B., Cain, K., Mosser, D. D., Mahboubi, A., Kuwana, T., Tailor, P., Morimoto, R. I., Cohen, G. M. and Green, D. R. (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2, 469–75.PubMedGoogle Scholar
  16. Bidmon, B., Endemann, M., Muller, T., Arbeiter, K., Herkner, K. and Aufricht, C. (2000) Heat shock protein-70 repairs proximal tubule structure after renal ischemia. Kidney Int 58, 2400–7.PubMedCrossRefGoogle Scholar
  17. Bidmon, B., Endemann, M., Muller, T., Arbeiter, K., Herkner, K. and Aufricht, C. (2002) HSP-25 and HSP-90 stabilize Na,K-ATPase in cytoskeletal fractions of ischemic rat renal cortex. Kidney Int 62, 1620–7.PubMedCrossRefGoogle Scholar
  18. Bonegio, R. and Lieberthal, W. (2002) Role of apoptosis in the pathogenesis of acute renal failure. Curr Opin Nephrol Hypertens 11, 301–8.PubMedCrossRefGoogle Scholar
  19. Bork, P., Sander, C. and Valencia, A. (1992) An ATPase domain common to prokaryotic cell cycle proteins, sugar kinases, actin, and hsp70 heat shock proteins. Proc Natl Acad Sci U S A 89, 7290–4.PubMedGoogle Scholar
  20. Borkan, S. C. and Gullans, S. R. (2002) Molecular chaperones in the kidney. Annu Rev Physiol 64, 503–27.PubMedCrossRefGoogle Scholar
  21. Borkan, S. C., Wang, Y. H., Lieberthal, W., Burke, P. R. and Schwartz, J. H. (1997) Heat stress ameliorates ATP depletion-induced sublethal injury in mouse proximal tubule cells. Am J Physiol 272, F347–55.PubMedGoogle Scholar
  22. Bortner, C. D. and Cidlowski, J. A. (1996) Absence of volume regulatory mechanisms contributes to the rapid activation of apoptosis in thymocytes. Am J Physiol 271, C950–61.PubMedGoogle Scholar
  23. Bortner, C. D. and Cidlowski, J. A. (1998) A necessary role for cell shrinkage in apoptosis. Biochem Pharmacol 56, 1549–59.PubMedCrossRefGoogle Scholar
  24. Brezis, M. and Epstein, F. H. (1993) Cellular mechanisms of acute ischemic injury in the kidney. Annu Rev Med 44, 27–37.PubMedCrossRefGoogle Scholar
  25. Bruce, J. L., Price, B. D., Coleman, C. N. and Calderwood, S. K. (1993) Oxidative injury rapidly activates the heat shock transcription factor but fails to increase levels of heat shock proteins. Cancer Res 53, 12–15.PubMedGoogle Scholar
  26. Burg, M. B., Ferraris, J. D. and Dmitrieva, N. I. (2007) Cellular response to hyperosmotic stresses. Physiol Rev 87, 1441–74.PubMedCrossRefGoogle Scholar
  27. Caruccio, L., Bae, S., Liu, A. Y. and Chen, K. Y. (1997) The heat-shock transcription factor HSF1 is rapidly activated by either hyper- or hypo-osmotic stress in mammalian cells. Biochem J 327 (Pt 2), 341–7.PubMedGoogle Scholar
  28. Chiang-Ting, C., Tzu-Ching, C., Ching-Yi, T., Song-Kuen, S. and Ming-Kuen, L. (2005) Adenovirus-mediated bcl-2 gene transfer inhibits renal ischemia/reperfusion induced tubular oxidative stress and apoptosis. Am J Transplant 5, 1194–203.PubMedCrossRefGoogle Scholar
  29. Chien, C. T., Lee, P. H., Chen, C. F., Ma, M. C., Lai, M. K. and Hsu, S. M. (2001) De novo demonstration and co-localization of free-radical production and apoptosis formation in rat kidney subjected to ischemia/reperfusion. J Am Soc Nephrol 12, 973–82.PubMedGoogle Scholar
  30. Chipuk, J. E., Bouchier-Hayes, L. and Green, D. R. (2006) Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario. Cell Death Differ 13, 1396–402.PubMedGoogle Scholar
  31. Cohen, D. M., Wasserman, J. C. and Gullans, S. R. (1991) Immediate early gene and HSP70 expression in hyperosmotic stress in MDCK cells. Am J Physiol 261, C594–601.PubMedGoogle Scholar
  32. Concannon, C. G., Gorman, A. M. and Samali, A. (2003) On the role of Hsp27 in regulating apoptosis. Apoptosis 8, 61–70.PubMedCrossRefGoogle Scholar
  33. Creagh, E. M., Carmody, R. J. and Cotter, T. G. (2000) Heat shock protein 70 inhibits caspase-dependent and -independent apoptosis in Jurkat T cells. Exp Cell Res 257, 58–66.PubMedCrossRefGoogle Scholar
  34. Daemen, M. A., van ‘t Veer, C., Denecker, G., Heemskerk, V. H., Wolfs, T. G., Clauss, M., Vandenabeele, P. and Buurman, W. A. (1999) Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation. J Clin Invest 104, 541–9.PubMedCrossRefGoogle Scholar
  35. DalleDonne, I., Milzani, A. and Colombo, R. (1997) Actin assembly by cadmium ions. Biochim Biophys Acta 1357, 5–17.PubMedCrossRefGoogle Scholar
  36. Danial, N. N. and Korsmeyer, S. J. (2004) Cell death: critical control points. Cell 116, 205–19.PubMedCrossRefGoogle Scholar
  37. Djamali, A., Reese, S., Oberley, T., Hullett, D. and Becker, B. (2005) Heat shock protein 27 in chronic allograft nephropathy: a local stress response. Transplantation 79, 1645–57.PubMedCrossRefGoogle Scholar
  38. Dmitrieva, N. I., Bulavin, D. V. and Burg, M. B. (2003) High NaCl causes Mre11 to leave the nucleus, disrupting DNA damage signaling and repair. Am J Physiol Renal Physiol 285, F266–F74.PubMedGoogle Scholar
  39. Dmitrieva, N. I., Cai, Q. and Burg, M. B. (2004) Cells adapted to high NaCl have many DNA breaks and impaired DNA repair both in cell culture and in vivo. Proc Natl Acad Sci U S A 101, 2317–22.PubMedCrossRefGoogle Scholar
  40. Doong, H., Vrailas, A. and Kohn, E. C. (2002) What’s in the ‘BAG’? – a functional domain analysis of the BAG-family proteins. Cancer Lett 188, 25–32.PubMedCrossRefGoogle Scholar
  41. Dragun, D., Hoff, U., Park, J. K., Qun, Y., Schneider, W., Luft, F. C. and Haller, H. (2000) Ischemia-reperfusion injury in renal transplantation is independent of the immunologic background. Kidney Int 58, 2166–77.PubMedCrossRefGoogle Scholar
  42. Eguchi, Y., Shimizu, S. and Tsujimoto, Y. (1997) Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res 57, 1835–40.PubMedGoogle Scholar
  43. Emami, A., Schwartz, J. H. and Borkan, S. C. (1991) Transient ischemia or heat stress induces a cytoprotectant protein in rat kidney. Am J Physiol 260, F479–85.PubMedGoogle Scholar
  44. Er, E., Oliver, L., Cartron, P. F., Juin, P., Manon, S. and Vallette, F. M. (2006) Mitochondria as the target of the pro-apoptotic protein Bax. Biochim Biophys Acta 1757, 1301–11.PubMedGoogle Scholar
  45. Fadeel, B. and Orrenius, S. (2005) Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease. J Intern Med 258, 479–517.PubMedCrossRefGoogle Scholar
  46. Fadeel, B., Zhivotovsky, B. and Orrenius, S. (1999) All along the watchtower: on the regulation of apoptosis regulators. Faseb J 13, 1647–57.PubMedGoogle Scholar
  47. Faubel, S., Ljubanovic, D., Reznikov, L., Somerset, H., Dinarello, C. A. and Edelstein, C. L. (2004) Caspase-1-deficient mice are protected against cisplatin-induced apoptosis and acute tubular necrosis. Kidney Int 66, 2202–13.PubMedCrossRefGoogle Scholar
  48. Forbes, J. M., Coughlan, M. T. and Cooper, M. E. (2008) Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 57, 1446–54.PubMedCrossRefGoogle Scholar
  49. Franco, D. L., Nojek, I. M., Molinero, L., Coso, O. A. and Costas, M. A. (2002) Osmotic stress sensitizes naturally resistant cells to TNF-alpha-induced apoptosis. Cell Death Differ 9, 1090–8.PubMedCrossRefGoogle Scholar
  50. Gabai, V. L., Mabuchi, K., Mosser, D. D. and Sherman, M. Y. (2002) Hsp72 and stress kinase c-jun N-terminal kinase regulate the bid-dependent pathway in tumor necrosis factor-induced apoptosis. Mol Cell Biol 22, 3415–24.PubMedCrossRefGoogle Scholar
  51. Gaudio, K. M., Thulin, G., Mann, A., Kashgarian, M. and Siegel, N. J. (1998) Role of heat stress response in the tolerance of immature renal tubules to anoxia. Am J Physiol 274, F1029–36.PubMedGoogle Scholar
  52. Goering, P. L., Fisher, B. R., Chaudhary, P. P. and Dick, C. A. (1992) Relationship between stress protein induction in rat kidney by mercuric chloride and nephrotoxicity. Toxicol Appl Pharmacol 113, 184–91.PubMedCrossRefGoogle Scholar
  53. Goering, P. L., Fisher, B. R., Noren, B. T., Papaconstantinou, A., Rojko, J. L. and Marler, R. J. (2000) Mercury induces regional and cell-specific stress protein expression in rat kidney. Toxicol Sci 53, 447–57.PubMedCrossRefGoogle Scholar
  54. Gotoh, T., Terada, K., Oyadomari, S. and Mori, M. (2004) hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria. Cell Death Differ 11, 390–402.PubMedCrossRefGoogle Scholar
  55. Granja, C., Moliterno, R. A., Ferreira, M. S., Fonseca, J. A., Kalil, J. and Coelho, V. (2004) T-cell autoreactivity to Hsp in human transplantation may involve both proinflammatory and regulatory functions. Hum Immunol 65, 124–34.PubMedCrossRefGoogle Scholar
  56. Greenberg, M. M. (2004) In vitro and in vivo effects of oxidative damage to deoxyguanosine. Biochem Soc Trans 32, 46–50.PubMedCrossRefGoogle Scholar
  57. Guisasola, M. C., Dulin, E., Almendral, J. and Garcia-Barreno, P. (2008) Reduction of heat shock protein antibody levels by statin therapy. Lipids 44, 317–24.PubMedGoogle Scholar
  58. Harrison, E. M., Sharpe, E., Bellamy, C. O., McNally, S. J., Devey, L., Garden, O. J., Ross, J. A. and Wigmore, S. J. (2008) Heat shock protein 90-binding agents protect renal cells from oxidative stress and reduce kidney ischemia-reperfusion injury. Am J Physiol Renal Physiol 295, F397–F405.PubMedCrossRefGoogle Scholar
  59. Havasi, A., Li, Z., Wang, Z., Martin, J. L., Botla, V., Ruchalski, K., Schwartz, J. H. and Borkan, S. C. (2008) Hsp27 inhibits Bax activation and apoptosis via a phosphatidylinositol 3-kinase-dependent mechanism. J Biol Chem 283, 12305–13.PubMedCrossRefGoogle Scholar
  60. Healy, D. A., Daly, P. J., Docherty, N. G., Murphy, M., Fitzpatrick, J. M. and Watson, R. W. (2006) Heat shock-induced protection of renal proximal tubular epithelial cells from cold storage and rewarming injury. J Am Soc Nephrol 17, 805–12.PubMedCrossRefGoogle Scholar
  61. Hensold, J. O., Hunt, C. R., Calderwood, S. K., Housman, D. E. and Kingston, R. E. (1990) DNA binding of heat shock factor to the heat shock element is insufficient for transcriptional activation in murine erythroleukemia cells. Mol Cell Biol 10, 1600–8.PubMedGoogle Scholar
  62. Heo, J. I., Lee, M. S., Kim, J. H., Lee, J. S., Kim, J., Park, J. B., Lee, J. Y., Han, J. A. and Kim, J. I. (2006) The role of tonicity responsive enhancer sites in the transcriptional regulation of human hsp70-2 in response to hypertonic stress. Exp Mol Med 38, 295–301.PubMedGoogle Scholar
  63. Hernadez-Pando, R., Pedraza-Chaverri, J., Orozco-Estevez, H., Silva-Serna, P., Moreno, I., Rondan-Zarate, A., Elinos, M., Correa-Rotter, R. and Larriva-Sahd, J. (1995) Histological and subcellular distribution of 65 and 70 kD heat shock proteins in experimental nephrotoxic injury. Exp Toxicol Pathol 47, 501–8.PubMedGoogle Scholar
  64. Jacobson, M. D., Weil, M. and Raff, M. C. (1997) Programmed cell death in animal development. Cell 88, 347–54.PubMedCrossRefGoogle Scholar
  65. Jani, A., Ljubanovic, D., Faubel, S., Kim, J., Mischak, R. and Edelstein, C. L. (2004) Caspase inhibition prevents the increase in caspase-3, -2, -8 and -9 activity and apoptosis in the cold ischemic mouse kidney. Am J Transplant 4, 1246–54.PubMedCrossRefGoogle Scholar
  66. Jo, S. K., Ko, G. J., Boo, C. S., Cho, W. Y. and Kim, H. K. (2006) Heat preconditioning attenuates renal injury in ischemic ARF in rats: role of heat-shock protein 70 on NF-kappaB-mediated inflammation and on tubular cell injury. J Am Soc Nephrol 17, 3082–92.PubMedCrossRefGoogle Scholar
  67. Jurivich, D. A., Sistonen, L., Kroes, R. A. and Morimoto, R. I. (1992) Effect of sodium salicylate on the human heat shock response. Science 255, 1243–5.PubMedCrossRefGoogle Scholar
  68. Kabakov, A. E. and Gabai, V. L. (1993) Protein aggregation as primary and characteristic cell reaction to various stresses. Experientia 49, 706–13.PubMedCrossRefGoogle Scholar
  69. Kelly, K. J. (2005) Heat shock (stress response) proteins and renal ischemia/reperfusion injury. Contrib Nephrol 148, 86–106.PubMedGoogle Scholar
  70. Kelly, K. J. (2006) Acute renal failure: much more than a kidney disease. Semin Nephrol 26, 105–13.PubMedCrossRefGoogle Scholar
  71. Kelly, K. J., Sandoval, R. M., Dunn, K. W., Molitoris, B. A. and Dagher, P. C. (2003) A novel method to determine specificity and sensitivity of the TUNEL reaction in the quantitation of apoptosis. Am J Physiol Cell Physiol 284, C1309–18.PubMedGoogle Scholar
  72. Kelly, K. J., Sutton, T. A., Weathered, N., Ray, N., Caldwell, E. J., Plotkin, Z. and Dagher, P. C. (2004) Minocycline inhibits apoptosis and inflammation in a rat model of ischemic renal injury. Am J Physiol Renal Physiol 287, F760–6.PubMedCrossRefGoogle Scholar
  73. Kim, M. S., Kim, B. J., Woo, H. N., Kim, K. W., Kim, K. B., Kim, I. K. and Jung, Y. K. (2000) Cadmium induces caspase-mediated cell death: suppression by Bcl-2. Toxicology 145, 27–37.PubMedCrossRefGoogle Scholar
  74. Komatsuda, A., Wakui, H., Satoh, K., Yasuda, T., Imai, H., Nakamoto, Y., Miura, A. B., Itoh, H. and Tashima, Y. (1993) Altered localization of 73-kilodalton heat-shock protein in rat kidneys with gentamicin-induced acute tubular injury. Lab Invest 68, 687–95.PubMedGoogle Scholar
  75. Korsmeyer, S. J. (1999) BCL-2 gene family and the regulation of programmed cell death. Cancer Res 59, 1693s–1700s.PubMedGoogle Scholar
  76. Kultz, D. and Chakravarty, D. (2001) Hyperosmolality in the form of elevated NaCl but not urea causes DNA damage in murine kidney cells. Proc Natl Acad Sci U S A 98, 1999–2004.PubMedCrossRefGoogle Scholar
  77. Kunduzova, O. R., Escourrou, G., Seguelas, M. H., Delagrange, P., De La Farge, F., Cambon, C. and Parini, A. (2003) Prevention of apoptotic and necrotic cell death, caspase-3 activation, and renal dysfunction by melatonin after ischemia/reperfusion. Faseb J 17, 872–4.PubMedGoogle Scholar
  78. Lang, K. S., Fillon, S., Schneider, D., Rammensee, H. G. and Lang, F. (2002) Stimulation of TNF alpha expression by hyperosmotic stress. Pflugers Arch 443, 798–803.PubMedGoogle Scholar
  79. Lee, H. T., Kim, M., Jan, M., Penn, R. B. and Emala, C. W. (2007) Renal tubule necrosis and apoptosis modulation by A1 adenosine receptor expression. Kidney Int 71, 1249–61.PubMedCrossRefGoogle Scholar
  80. Lee, J. S., Lee, J. J. and Seo, J. S. (2005) HSP70 deficiency results in activation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, and caspase-3 in hyperosmolarity-induced apoptosis. J Biol Chem 280, 6634–41.PubMedGoogle Scholar
  81. Levine, R. L. (2002) Carbonyl modified proteins in cellular regulation, aging, and disease. Free Radic Biol Med 32, 790–6.PubMedCrossRefGoogle Scholar
  82. Levine, R. L., Wehr, N., Williams, J. A., Stadtman, E. R. and Shacter, E. (2000) Determination of carbonyl groups in oxidized proteins. Methods Mol Biol 99, 15–24.PubMedGoogle Scholar
  83. Li, C., Lee, J., Ko, Y., Kim, J. and Seo, J. (2000) Heat shock protein 70 inhibits apoptosis downstream of cytochrome c release and upstream of caspase 3 activation. J Biol Chem 275, 25665–71.PubMedGoogle Scholar
  84. Li, F., Mao, H. P., Ruchalski, K. L., Wang, Y. H., Choy, W., Schwartz, J. H. and Borkan, S. C. (2002) Heat stress prevents mitochondrial injury in ATP-depleted renal epithelial cells. Am J Physiol Cell Physiol 283, C917–26.PubMedGoogle Scholar
  85. Lieberthal, W., Menza, S. A. and Levine, J. S. (1998) Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells. Am J Physiol 274, F315–27.PubMedGoogle Scholar
  86. Lindsten, T., Ross, A. J., King, A., Zong, W. X., Rathmell, J. C., Shiels, H. A., Ulrich, E., Waymire, K. G., Mahar, P., Frauwirth, K., Chen, Y., Wei, M., Eng, V. M., Adelman, D. M., Simon, M. C., Ma, A., Golden, J. A., Evan, G., Korsmeyer, S. J., MacGregor, G. R. and Thompson, C. B. (2000) The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell 6, 1389–99.PubMedCrossRefGoogle Scholar
  87. Maeno, E., Ishizaki, Y., Kanaseki, T., Hazama, A. and Okada, Y. (2000) Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proc Natl Acad Sci U S A 97, 9487–92.PubMedCrossRefGoogle Scholar
  88. Manucha, W., Carrizo, L., Ruete, C., Molina, H and Vellés, P. (2005) Angiotensin II type I antagonist on oxidative stress and heat shock protien 70 (HSP 70) expression in obstructive nephropathy. Cell Mol Biol 6, 547–55.Google Scholar
  89. Mao, H., Li, Z., Zhou, Y., Zhuang, S., An, X., Zhang, B., Chen, W., Nie, J., Wang, Z., Borkan, S. C., Wang, Y. and Yu, X. (2008) HSP72 attenuates renal tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy. Am J Physiol Renal Physiol 295, F202–14.PubMedCrossRefGoogle Scholar
  90. Mao, H., Wang, Y., Li, Z., Ruchalski, K. L., Yu, X., Schwartz, J. H. and Borkan, S. C. (2004) Hsp72 interacts with paxillin and facilitates the reassembly of focal adhesions during recovery from ATP depletion. J Biol Chem 279, 15472–80.PubMedGoogle Scholar
  91. Margulis, B. A. and Welsh, M. (1991) Isolation of hsp70-binding proteins from bovine muscle. Biochem Biophys Res Commun 178, 1–7.PubMedCrossRefGoogle Scholar
  92. Meldrum, K. K., Meldrum, D. R., Sezen, S. F., Crone, J. K. and Burnett, A. L. (2001) Heat shock prevents simulated ischemia-induced apoptosis in renal tubular cells via a PKC-dependent mechanism. Am J Physiol Regul Integr Comp Physiol 281, R359–64.PubMedGoogle Scholar
  93. Michea, L., Combs, C., Andrews, P., Dmitrieva, N. and Burg, M. B. (2002) Mitochondrial dysfunction is an early event in high-NaCl-induced apoptosis of mIMCD3 cells. Am J Physiol Renal Physiol 282, F981–90.PubMedGoogle Scholar
  94. Michea, L., Ferguson, D. R., Peters, E. M., Andrews, P. M., Kirby, M. R. and Burg, M. B. (2000) Cell cycle delay and apoptosis are induced by high salt and urea in renal medullary cells. Am J Physiol Renal Physiol 278, F209–18.PubMedGoogle Scholar
  95. Mifflin, L. C. and Cohen, R. E. (1994) Characterization of denatured protein inducers of the heat shock (stress) response in Xenopus laevis oocytes. J Biol Chem 269, 15710–7.PubMedGoogle Scholar
  96. Mikhailov, V., Mikhailova, M., Degenhardt, K., Venkatachalam, M. A., White, E. and Saikumar, P. (2003) Association of Bax and Bak homo-oligomers in mitochondria. Bax requirement for Bak reorganization and cytochrome c release. J Biol Chem 278, 5367–76.PubMedCrossRefGoogle Scholar
  97. Mikhailov, V., Mikhailova, M., Pulkrabek, D. J., Dong, Z., Venkatachalam, M. A. and Saikumar, P. (2001) Bcl-2 prevents Bax oligomerization in the mitochondrial outer membrane. J Biol Chem 276, 18361–74.PubMedCrossRefGoogle Scholar
  98. Molitoris, B. A. (1991) Ischemia-induced loss of epithelial polarity: potential role of the actin cytoskeleton. Am J Physiol 260, F769–78.PubMedGoogle Scholar
  99. Molitoris, B. A., Geerdes, A. and McIntosh, J. R. (1991) Dissociation and redistribution of Na+,K(+)-ATPase from its surface membrane actin cytoskeletal complex during cellular ATP depletion. J Clin Invest 88, 462–9.PubMedCrossRefGoogle Scholar
  100. Molitoris, B. A., Leiser, J. and Wagner, M. C. (1997) Role of the actin cytoskeleton in ischemia-induced cell injury and repair. Pediatr Nephrol 11, 761–7.PubMedCrossRefGoogle Scholar
  101. Molitoris, B. A. and Marrs, J. (1999) The role of cell adhesion molecules in ischemic acute renal failure. Am J Med 106, 583–92.PubMedCrossRefGoogle Scholar
  102. Morimoto, R. I. (1998) Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 12, 3788–96.PubMedCrossRefGoogle Scholar
  103. Moseley, P. (2000) Stress proteins and the immune response. Immunopharmacology 48, 299–302.PubMedCrossRefGoogle Scholar
  104. Mosser, D. D., Caron, A. W., Bourget, L., Meriin, A. B., Sherman, M. Y., Morimoto, R. I. and Massie, B. (2000) The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Mol Cell Biol 20, 7146–59.PubMedGoogle Scholar
  105. Mueller, T., Regele, H., Posch, M., Marszalek, M., Schwarz, C., Pichlhoefer, B., Arbeiter, K. and Aufricht, C. (2004) HSP-72 expression in pre-transplant donor kidney biopsies and post-transplant outcome. Transplantation 78, 292–5.PubMedGoogle Scholar
  106. Nakada, J., Matsura, T., Okazaki, N., Nishida, T., Togawa, A., Minami, Y., Inagaki, Y., Ito, H., Yamada, K. and Ishibe, Y. (2005) Oral administration of geranylgeranylacetone improves survival rate in a rat endotoxin shock model: administration timing and heat shock protein 70 induction. Shock 24, 482–7.PubMedCrossRefGoogle Scholar
  107. Nath, K. A., Croatt, A. J., Likely, S., Behrens, T. W. and Warden, D. (1996) Renal oxidant injury and oxidant response induced by mercury. Kidney Int 50, 1032–43.PubMedCrossRefGoogle Scholar
  108. Neuhofer, W., Lugmayr, K., Fraek, M. L. and Beck, F. X. (2001) Regulated overexpression of heat shock protein 72 protects Madin-Darby canine kidney cells from the detrimental effects of high urea concentrations. J Am Soc Nephrol 12, 2565–71.PubMedGoogle Scholar
  109. Neuhofer, W., Muller, E., Burger-Kentischer, A., Fraek, M. L., Thurau, K. and Beck, F. X. (1999) Inhibition of NaCl-induced heat shock protein 72 expression renders MDCK cells susceptible to high urea concentrations. Pflugers Arch 437, 611–6.PubMedCrossRefGoogle Scholar
  110. Oberbauer, R., Schwarz, C., Regele, H. M., Hansmann, C., Meyer, T. W. and Mayer, G. (2001) Regulation of renal tubular cell apoptosis and proliferation after ischemic injury to a solitary kidney. J Lab Clin Med 138, 343–51.PubMedCrossRefGoogle Scholar
  111. Ogawa, F., Shimizu, K., Hara, T., Muroi, E., Hasegawa, M., Takehara, K. and Sato, S. (2008) Serum levels of heat shock protein 70, a biomarker of cellular stress, are elevated in patients with systemic sclerosis: association with fibrosis and vascular damage. Clin Exp Rheumatol 26, 659–62.PubMedGoogle Scholar
  112. Okada, Y., Maeno, E., Shimizu, T., Dezaki, K., Wang, J. and Morishima, S. (2001) Receptor-mediated control of regulatory volume decrease (RVD) and apoptotic volume decrease (AVD). J Physiol 532, 3–16.PubMedCrossRefGoogle Scholar
  113. Ortiz, P. A., Hong, N. J. and Garvin, J. L. (2004) Luminal flow induces eNOS activation and translocation in the rat thick ascending limb. II. Role of PI3-kinase and Hsp90. Am J Physiol Renal Physiol 287, F281–8.PubMedGoogle Scholar
  114. Ortiz, A., Justo, P., Sanz, A., Lorz, C. and Egido, J. (2003) Targeting apoptosis in acute tubular injury. Biochem Pharmacol 66, 1589–4.CrossRefGoogle Scholar
  115. Ortiz, A., Lorz, C., Catalan, M. P., Danoff, T. M., Yamasaki, Y., Egido, J. and Neilson, E. G. (2000) Expression of apoptosis regulatory proteins in tubular epithelium stressed in culture or following acute renal failure. Kidney Int 57, 969–81.PubMedCrossRefGoogle Scholar
  116. Ortiz, A., Lorz, C., Justo, P., Catalan, M. P. and Egido, J. (2001) Contribution of apoptotic cell death to renal injury. J Cell Mol Med 5, 18–32.PubMedCrossRefGoogle Scholar
  117. Paul, C., Manero, F., Gonin, S., Kretz-Remy, C., Virot, S. and Arrigo, A. P. (2002) Hsp27 as a negative regulator of cytochrome C release. Mol Cell Biol 22, 816–34.PubMedCrossRefGoogle Scholar
  118. Perdrizet, G. A., Kaneko, H., Buckley, T. M., Fishman, M. S., Pleau, M., Bow, L. and Schweizer, R. T. (1993) Heat shock and recovery protects renal allografts from warm ischemic injury and enhances HSP72 production. Transplant Proc 25, 1670–3.PubMedGoogle Scholar
  119. Petronini, P. G., Alfieri, R., De Angelis, E., Campanini, C., Borghetti, A. F. and Wheeler, K. P. (1993) Different HSP70 expression and cell survival during adaptive responses of 3T3 and transformed 3T3 cells to osmotic stress. Br J Cancer 67, 493–9.PubMedCrossRefGoogle Scholar
  120. Poccia, F., Piselli, P., Vendetti, S., Bach, S., Amendola, A., Placido, R. and Colizzi, V. (1996) Heat-shock protein expression on the membrane of T cells undergoing apoptosis. Immunology 88, 6–12.PubMedCrossRefGoogle Scholar
  121. Prakash, J., Vohra, R., Wani, I. A., Murthy, A. S., Srivastva, P. K., Tripathi, K., Pandey, L. K., Usha, R.L and Raja, R. (2007) Decreasing incidence of renal cortical necrosis in patients with acute renal failure in developing countries: a single-centre experience of 22 years from Eastern India. Nephrol Dial Transplant 22, 1213–7.PubMedGoogle Scholar
  122. Puthalakath, H., Huang, D. C., O’Reilly, L. A., King, S. M. and Strasser, A. (1999) The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell 3, 287–96.PubMedCrossRefGoogle Scholar
  123. Racusen, L. C. (1998) Epithelial cell shedding in acute renal injury. Clin Exp Pharmacol Physiol 25, 273–5.PubMedCrossRefGoogle Scholar
  124. Ran, R., Zhou, G., Lu, A., Zhang, L., Tang, Y., Rigby, A. C. and Sharp, F. R. (2004) Hsp70 mutant proteins modulate additional apoptotic pathways and improve cell survival. Cell Stress Chaperones 9, 229–42.PubMedCrossRefGoogle Scholar
  125. Rauchman, M. I., Pullman, J. and Gullans, S. R. (1997) Induction of molecular chaperones by hyperosmotic stress in mouse inner medullary collecting duct cells. Am J Physiol 273, F9–17.PubMedGoogle Scholar
  126. Ravagnan, L., Gurbuxani, S., Susin, S. A., Maisse, C., Daugas, E., Zamzami, N., Mak, T., Jaattela, M., Penninger, J. M., Garrido, C. and Kroemer, G. (2001) Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nat Cell Biol 3, 839–43.PubMedCrossRefGoogle Scholar
  127. Rosen, S. and Heyman, S. N. (2001) Difficulties in understanding human “acute tubular necrosis”: limited data and flawed animal models. Kidney Int 60, 1220–4.PubMedCrossRefGoogle Scholar
  128. Rosette, C. and Karin, M. (1996) Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors. Science 274, 1194–7.PubMedCrossRefGoogle Scholar
  129. Ruchalski, K., Mao, H., Li, Z., Wang, Z., Gillers, S., Wang, Y., Mosser, D. D., Gabai, V., Schwartz, J. H. and Borkan, S. C. (2006) Distinct hsp70 domains mediate apoptosis-inducing factor release and nuclear accumulation. J Biol Chem 281, 7873–80.PubMedCrossRefGoogle Scholar
  130. Ruchalski, K., Mao, H., Singh, S. K., Wang, Y., Mosser, D. D., Li, F., Schwartz, J. H. and Borkan, S. C. (2003) HSP72 inhibits apoptosis-inducing factor release in ATP-depleted renal epithelial cells. Am J Physiol Cell Physiol 285, C1483–93.PubMedGoogle Scholar
  131. Ryhanen, T., Hyttinen, J. M., Kopitz, J., Rilla, K., Kuusisto, E., Mannermaa, E., Viiri, J., Holmberg, C. I., Immonen, I., Meri, S., Parkkinen, J., Eskelinen, E. L., Uusitalo, H., Salminen, A. and Kaarniranta, K. (2008) Crosstalk between Hsp70 molecular chaperone, lysosomes and proteasomes in autophagy-mediated proteolysis in human retinal pigment epithelial cells. J Cell Mol Med. (Epub ahead of print)Google Scholar
  132. Saikumar, P., Dong, Z., Patel, Y., Hall, K., Hopfer, U., Weinberg, J. M. and Venkatachalam, M. A. (1998) Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene 17, 3401–15.PubMedGoogle Scholar
  133. Saikumar, P. and Venkatachalam, M. A. (2003) Role of apoptosis in hypoxic/ischemic damage in the kidney. Semin Nephrol 23, 511–21.PubMedCrossRefGoogle Scholar
  134. Santos, B. C., Chevaile, A., Hebert, M. J., Zagajeski, J. and Gullans, S. R. (1998a) A combination of NaCl and urea enhances survival of IMCD cells to hyperosmolality. Am J Physiol 274, F1167–73.PubMedGoogle Scholar
  135. Santos, B. C., Chevaile, A., Hebert, M. J., Zagajeski, J. and Gullans, S. R. (1998b) A combination of NaCl and urea enhances survival of IMCD cells to hyperosmolality. Am J Physiol 274, F1167–73.PubMedGoogle Scholar
  136. Sarge, K. D., Murphy, S. P. and Morimoto, R. I. (1993) Activation of heat shock gene transcription by heat shock factor 1 involves oligomerization, acquisition of DNA-binding activity, and nuclear localization and can occur in the absence of stress. Mol Cell Biol 13, 1392–407.PubMedGoogle Scholar
  137. Schober, A., Burger-Kentischer, A., Muller, E. and Beck, F. X. (1998) Effect of ischemia on localization of heat shock protein 25 in kidney. Kidney Int Suppl 67, S174–6.PubMedGoogle Scholar
  138. Schumer, M., Colombel, M. C., Sawczuk, I. S., Gobe, G., Connor, J., O’Toole, K. M., Olsson, C. A., Wise, G. J. and Buttyan, R. (1992) Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia. Am J Pathol 140, 831–8.PubMedGoogle Scholar
  139. Shelden, E. A., Borrelli, M. J., Pollock, F. M. and Bonham, R. (2002) Heat shock protein 27 associates with basolateral cell boundaries in heat-shocked and ATP-depleted epithelial cells. J Am Soc Nephrol 13, 332–41.PubMedCrossRefGoogle Scholar
  140. Shim, E. H., Kim, J. I., Bang, E. S., Heo, J. S., Lee, J. S., Kim, E. Y., Lee, J. E., Park, W. Y., Kim, S. H., Kim, H. S., Smithies, O., Jang, J. J., Jin, D. I. and Seo, J. S. (2002) Targeted disruption of hsp70.1 sensitizes to osmotic stress. EMBO Rep 3, 857–61.PubMedCrossRefGoogle Scholar
  141. Smoyer, W. E. and Ransom, R. F. (2002) Hsp27 regulates podocyte cytoskeletal changes in an in vitro model of podocyte process retraction. FASEB J 16, 315–26.PubMedCrossRefGoogle Scholar
  142. Spandou, E., Tsouchnikas, I., Karkavelas, G., Dounousi, E., Simeonidou, C., Guiba-Tziampiri, O. and Tsakiris, D. (2006) Erythropoietin attenuates renal injury in experimental acute renal failure ischaemic/reperfusion model. Nephrol Dial Transplant 21, 330–6.PubMedGoogle Scholar
  143. Stankiewicz, A. R., Lachapelle, G., Foo, C. P., Radicioni, S. M. and Mosser, D. D. (2005) Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation. J Biol Chem 280, 38729–39.PubMedCrossRefGoogle Scholar
  144. Steel, R., Doherty, J. P., Buzzard, K., Clemons, N., Hawkins, C. J. and Anderson, R. L. (2004) Hsp72 inhibits apoptosis upstream of the mitochondria and not through interactions with Apaf-1. J Biol Chem 279, 51490–9.PubMedCrossRefGoogle Scholar
  145. Sutton, T. A., Fisher, C. J. and Molitoris, B. A. (2002) Microvascular endothelial injury and dysfunction during ischemic acute renal failure. Kidney Int 62, 1539–49.PubMedCrossRefGoogle Scholar
  146. Suzuki, S., Maruyama, S., Sato, W., Morita, Y., Sato, F., Miki, Y., Kato, S., Katsuno, M., Sobue, G., Yuzawa, Y. and Matsuo, S. (2005) Geranylgeranylacetone ameliorates ischemic acute renal failure via induction of Hsp70. Kidney Int 67, 2210–20.PubMedCrossRefGoogle Scholar
  147. Tang, H. L., Le, A. H. and Lung, H. L. (2006) The increase in mitochondrial association with actin precedes Bax translocation in apoptosis. Biochem J 396, 1–5.PubMedGoogle Scholar
  148. Trieb, K., Grubeck-Loebenstein, B., Eberl, T. and Margreiter, R. (1996) T cells from rejected human kidney allografts respond to heat shock protein 72. Transpl Immunol 4, 43–5.PubMedCrossRefGoogle Scholar
  149. Turman, M. A., Kahn, D. A., Rosenfeld, S. L., Apple, C. A. and Bates, C. M. (1997) Characterization of human proximal tubular cells after hypoxic preconditioning: constitutive and hypoxia-induced expression of heat shock proteins HSP70 (A, B, and C), HSC70, and HSP90. Biochem Mol Med 60, 49–58.PubMedCrossRefGoogle Scholar
  150. van de Water, B., de Graauw, M., Le Devedec, S. and Alderliesten, M. (2006) Cellular stress responses and molecular mechanisms of nephrotoxicity. Toxicol Lett 162, 83–93.PubMedGoogle Scholar
  151. Van Why, S. K., Mann, A. S., Ardito, T., Thulin, G., Ferris, S., Macleod, M. A., Kashgarian, M. and Siegel, N. J. (2003) Hsp27 associates with actin and limits injury in energy depleted renal epithelia. J Am Soc Nephrol 14, 98–106.PubMedGoogle Scholar
  152. Van Why, S. K., Mann, A. S., Thulin, G., Zhu, X. H., Kashgarian, M. and Siegel, N. J. (1994) Activation of heat-shock transcription factor by graded reductions in renal ATP, in vivo, in the rat. J Clin Invest 94, 1518–23.PubMedGoogle Scholar
  153. Wang, Y. H. and Borkan, S. C. (1996) Prior heat stress enhances survival of renal epithelial cells after ATP depletion. Am J Physiol 270, F1057–65.PubMedGoogle Scholar
  154. Wang, Y., Knowlton, A. A., Christensen, T. G., Shih, T. and Borkan, S. C. (1999) Prior heat stress inhibits apoptosis in adenosine triphosphate-depleted renal tubular cells. Kidney Int 55, 2224–35.PubMedGoogle Scholar
  155. Waterhouse, N. J., Ricci, J. E. and Green, D. R. (2002) And all of a sudden it’s over: mitochondrial outer-membrane permeabilization in apoptosis. Biochimie 84, 113–21.PubMedCrossRefGoogle Scholar
  156. Wehner, F., Olsen, H., Tinel, H., Kinne-Saffran, E. and Kinne, R. K. (2003) Cell volume regulation: osmolytes, osmolyte transport, and signal transduction. Rev Physiol Biochem Pharmacol 148, 1–80.PubMedGoogle Scholar
  157. Wei, Q., Alam, M. M., Wang, M. H., Yu, F. and Dong, Z. (2004) Bid activation in kidney cells following ATP depletion in vitro and ischemia in vivo. Am J Physiol Renal Physiol 286, F803–9.PubMedCrossRefGoogle Scholar
  158. Wei, Q., Yin, X. M., Wang, M. H. and Dong, Z. (2006) Bid deficiency ameliorates ischemic renal failure and delays animal death in C57BL/6 mice. Am J Physiol Renal Physiol 290, F35–42.PubMedGoogle Scholar
  159. Wei, M. C., Zong, W. X., Cheng, E. H., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B. and Korsmeyer, S. J. (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292, 727–30.PubMedGoogle Scholar
  160. Weiss, R. A., Madaio, M. P., Tomaszewski, J. E. and Kelly, C. J. (1994) T cells reactive to an inducible heat shock protein induce disease in toxin-induced interstitial nephritis. J Exp Med 180, 2239–50.PubMedGoogle Scholar
  161. Wolfs, T. G., de Vries, B., Walter, S. J., Peutz-Kootstra, C. J., van Heurn, L. W., Oosterhof, G. O. and Buurman, W. A. (2005) Apoptotic cell death is initiated during normothermic ischemia in human kidneys. Am J Transplant 5, 68–75.PubMedCrossRefGoogle Scholar
  162. Womer, K. L., Vella, J. P. and Sayegh, M. H. (2000) Chronic allograft dysfunction: mechanisms and new approaches to therapy. Semin Nephrol 20, 126–47.PubMedGoogle Scholar
  163. Woo, S. K., Lee, S. D., Na, K. Y., Park, W. K. and Kwon, H. M. (2002) TonEBP/NFAT5 stimulates transcription of HSP70 in response to hypertonicity. Mol Cell Biol 22, 5753–60.PubMedCrossRefGoogle Scholar
  164. Wright, B. H., Corton, J. M., El-Nahas, A. M., Wood, R. F. and Pockley, A. G. (2000) Elevated levels of circulating heat shock protein 70 (Hsp70) in peripheral and renal vascular disease. Heart Vessels 15, 18–22.PubMedCrossRefGoogle Scholar
  165. Xue, F., Isaka, Y., Takahara, T., Imamura, R., Suzuki, C., Ichimaru, N., Michieli, P. and Takahara, S. (2007) HGF-MSP chimera protects kidneys from ischemia-reperfusion injury. Biochem Biophys Res Commun 363, 451–6.PubMedCrossRefGoogle Scholar
  166. Yaglom, J. A., Ekhterae, D., Gabai, V. L. and Sherman, M. Y. (2003) Regulation of necrosis of H9c2 myogenic cells upon transient energy deprivation. Rapid deenergization of mitochondria precedes necrosis and is controlled by reactive oxygen species, stress kinase JNK, HSP72 and ARC. J Biol Chem 278, 50483–96.PubMedCrossRefGoogle Scholar
  167. Yaglom, J. A., Gabai, V. L., Meriin, A. B., Mosser, D. D. and Sherman, M. Y. (1999) The function of HSP72 in suppression of c-Jun N-terminal kinase activation can be dissociated from its role in prevention of protein damage. J Biol Chem 274, 20223–8.PubMedCrossRefGoogle Scholar
  168. Yang, C. W., Ahn, H. J., Han, H. J., Kim, W. Y., Li, C., Shin, M. J., Kim, S. K., Park, J. H., Kim, Y. S., Moon, I. S. and Bang, B. K. (2001) Pharmacological preconditioning with low-dose cyclosporine or FK506 reduces subsequent ischemia/reperfusion injury in rat kidney. Transplantation 72, 1753–9.PubMedCrossRefGoogle Scholar
  169. Yang, E. and Korsmeyer, S. J. (1996) Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood 88, 386–401.PubMedGoogle Scholar
  170. Yang, C. W., Li, C., Jung, J. Y., Shin, S. J., Choi, B. S., Lim, S. W., Sun, B. K., Kim, Y. S., Kim, J., Chang, Y. S. and Bang, B. K. (2003) Preconditioning with erythropoietin protects against subsequent ischemia-reperfusion injury in rat kidney. Faseb J 17, 1754–5.PubMedCrossRefGoogle Scholar
  171. Zamzami, N. and Kroemer, G. (2001) OPINIONThe mitochondrion in apoptosis: how Pandora’s box opens. Nat Rev Mol Cell Biol 2, 67–71.PubMedCrossRefGoogle Scholar
  172. Zhang, Z., Dmitrieva, N. I., Park, J. H., Levine, R. L. and Burg, M. B. (2004) High urea and NaCl carbonylate proteins in renal cells in culture and in vivo, and high urea causes 8-oxoguanine lesions in their DNA. Proc Natl Acad Sci U S A 101, 9491–6.PubMedGoogle Scholar
  173. Zhang, P. L., Lun, M., Schworer, C. M., Blasick, T. M., Masker, K. K., Jones, J. B. and Carey, D. J. (2008) Heat shock protein expression is highly sensitive to ischemia-reperfusion injury in rat kidneys. Ann Clin Lab Sci 38, 57–64.PubMedGoogle Scholar
  174. Zuo, J., Rungger, D. and Voellmy, R. (1995) Multiple layers of regulation of human heat shock transcription factor 1. Mol Cell Biol 15, 4319–30.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Andrea Havasi
    • 1
  • Jonathan M. Gall
    • 1
  • Steven C. Borkan
    • 2
    Email author
  1. 1.Renal SectionBoston Medical Center, Evans Biomedical Research Center, Boston University School of MedicineBostonUSA
  2. 2.Renal SectionBoston Medical Center, Evans Biomedical Research Center, Boston University School of MedicineBostonUSA

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