Induction of heat-shock proteins does not prevent renal tubular injury following ischemia

Abstract

The possible protective effect of heat-shock proteins (HSPs) on ischemic injury to renal cells was assessed in two different experimental models: ischemia-reflow in intact rats and medullary hypoxic injury as seen in the isolated perfused rat kidney. Heat shock was induced by raising the core temperature of rats to 42 degrees C for 15 minutes. Following this, Northern blots showed enhanced gene expression of HSP70, HSP60 and ubiquitin at one hour and reaching a maximum by six hours after heat shock in all regions of the kidney, but most prominently in medulla and papilla. The HSP70 protein in the kidney, estimated by immunohistochemical means, was detectable 24 hours following heat shock and further increased at 48 hours following heat shock. In the first set of experiments, the animals underwent uninephrectomy followed by cross clamping of the remaining renal artery for 40 minutes prior to reflow. Serum creatinine and urea nitrogen rose to 3.15 +/- 0.98 and 126.4 +/- 62.5 mg/dl at 24 hours. No significant differences were observed at 24, 48 and 72 hours after reflow between these values in control rats and rats pretreated with heat shock 48 hours earlier. Severe morphological damage to proximal tubules of the renal cortex was observed to the same extent in both groups. In a second set of experiments, the right kidney was removed either 24 or 48 hours after heat shock and perfused in isolation for 90 minutes. Functional and morphological parameters were compared with those of isolated perfused kidneys obtained from animals that had not been subjected to heat shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Ischemic Conditioning Prevents Na,K-ATPase Dissociation from the Cytoskeletal Cellular Fraction after Repeat Renal Ischemia in Rats

“…In contrast, heat pretreatment did not protect morphology or global function against experimental renal ischemia in isolated perfused kidneys or proximal tubules, despite comparable induction of 70-kD HSP (15,16). Interestingly, however, heat-conditioned kidneys demonstrated significant preservation of sodium reabsorption (15).…”

“…In contrast, heat pretreatment did not protect morphology or global function against experimental renal ischemia in isolated perfused kidneys or proximal tubules, despite comparable induction of 70-kD HSP (15,16). Interestingly, however, heat-conditioned kidneys demonstrated significant preservation of sodium reabsorption (15). As the authors did not assess cellular localization or distribution of Na,K-ATPase in proximal tubule cells, it could be that the heat pretreatment resulted in an unappreciated preservation of Na,K-ATPase polarity and function, thus preserving sodium reabsorptive ability.…”

Inducible Nitric-oxide Synthase Is an Important Contributor to Prolonged Protective Effects of Ischemic Preconditioning in the Mouse Kidney

“…HSPs confer cytoprotection against ischemia, ATP depletion or reactive oxygen species in many organs and cultured cells through stabilization of the actin cytoskeleton and/or reduction of the inflammatory reaction (51)(52)(53)(54). We also reported that the overexpression of HSP-25 protein in renal epithelial LLC-PK1 cells using adenoviral vectors protects cells from injury due to oxidants and chemical anoxia (6).…”

Hsp27 Associates with Actin and Limits Injury in Energy Depleted Renal Epithelia

“…Whole animal studies using heat preconditioning showed minimal cross-tolerance to subsequent ischemic or hypoxic injury (19,20). Ischemic preconditioning protected against a subsequent hypoxic insult but was not well correlated with HSP synthesis (19).…”