Multifaceted Role of Heat Stress Proteins in the Kidney

Abstract

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