title: Heat shock prevents simulated ischemia-induced apoptosis in renal tubular cells via a PKC-dependent mechanism.
abstract: Heat shock produces cellular tolerance to a variety of adverse conditions; however, the protective effect of heat shock on renal cell ischemic injury remains unclear. Protein kinase C (PKC) has been implicated in the signaling mechanisms of acute preconditioning, yet it remains unknown whether PKC mediates heat shock-induced delayed preconditioning in renal cells. To study this, renal tubular cells (LLC-PK1) were exposed to thermal stress (43 degrees C) for 1 h and heat shock protein (HSP) 72 induction was confirmed by Western blot analysis. Cells were subjected to simulated ischemia 24 h after thermal stress, and the effect of heat shock (delayed preconditioning) on ischemia-induced apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling) and B cell lymphoma 2 (Bcl(2)) expression (Western) was determined. Subsequently, the effect of PKC inhibition on HSP72 induction and heat stress-induced ischemic tolerance was evaluated. Thermal stress induced HSP72 production, increased Bcl(2) expression, and prevented simulated ischemia-induced renal tubular cell apoptosis. PKC inhibition abolished thermal induction of HSP72 and prevented heat stress-induced ischemic tolerance. These data demonstrate that thermal stress protects renal tubular cells from simulated ischemia-induced apoptosis through a PKC-dependent mechanism.
authors.affiliation: Departments of Urology and Surgery, Johns Hopkins University, Baltimore, Maryland 21287, USA. kirstan@earthlink.net
authors.forename: K K
authors.initials: KK
authors.lastname: Meldrum
authors.forename: D R
authors.initials: DR
authors.lastname: Meldrum
authors.forename: S F
authors.initials: SF
authors.lastname: Sezen
authors.forename: J K
authors.initials: JK
authors.lastname: Crone
authors.forename: A L
authors.initials: AL
authors.lastname: Burnett
mesh_terms: D000470:Alkaloids; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053119:Benzophenanthridines; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D006358:Hot Temperature; D007211:Indoles / Q000494:pharmacology; D007511:Ischemia / Q000473:pathology*; D019194:Ischemic Preconditioning; D018374:LLC-PK1 Cells; D008301:Maleimides / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism; D013552:Swine
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007211:Indoles; D008301:Maleimides; D010617:Phenanthridines; D019253:Proto-Oncogene Proteins c-bcl-2; C016299:chelerythrine; D011493:Protein Kinase C; C088060:bisindolylmaleimide