Prior heat stress enhances survival of renal epithelial cells after ATP depletion.
The 72-kDa heat stress protein (HSP-72) is an inducible cytoprotectant protein. Although transient renal ischemia in vivo induces HSP-72, it is not known whether prior heat stress protects renal epithelial cells from injury mediated by ATP depletion. To evaluate this hypothesis, opossum kidney (OK) cells were exposed to sodium cyanide and 2-deoxy-D-glucose in the absence of medium glucose, a maneuver that reduced cell ATP content to < 10% of the control value within 10 min and decreased cell survival. One day after 2 h of ATP depletion, OK cells previously exposed to heat stress (to induce accumulation of HSP-72) exhibited marked improvement in survival (a > 4-fold increase in total DNA), less uptake of vital dye, and less release of lactate dehydrogenase (LDH) than cells subjected to ATP depletion alone (23.0 +/- 1.6 vs. 34.1 +/- 1.2% of total LDH, respectively). Enhanced clonogenicity post-heat stress was completely prevented by cycloheximide and positively correlated with the steady-state content of HSP-72. In the recovery period after ATP depletion, cell ATP content, maximum mitochondrial ATP production rate, and total LDH activity were all significantly higher in cells with abundant HSP-72. Although the protective effects associated with heat stress are likely to be multifactoral, preserved cell metabolism and higher ATP content could enhance cellular repair processes after ATP depletion.
Wang
Y H
YH
Thorndike Memorial Laboratory, Boston University Medical Center, Boston City Hospital, Massachusetts 02118, USA.
Borkan
S C
SC
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003513:Cycloheximide / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D050884:HSP72 Heat-Shock Proteins; D018882:Heat Stress Disorders / Q000378:metabolism / Q000473:pathology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009893:Opossums; D012966:Sodium Cyanide / Q000494:pharmacology
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D000255:Adenosine Triphosphate; D003513:Cycloheximide; D003847:Deoxyglucose; D007770:L-Lactate Dehydrogenase; D012966:Sodium Cyanide