Mediators and mechanisms of heat shock protein 70 based cytoprotection in obstructive nephropathy

Abstract

Urinary heat shock protein 70 (Hsp70) is rapidly increased in patients with clinical acute kidney injury, indicating that it constitutes a component of the endogenous stress response to renal injury. Moreover, experimental models have demonstrated that Hsp70 activation is associated with the cytoprotective actions of several drugs following obstruction, including nitric oxide (NO) donors, geranylgeranylacetone, vitamin D, and rosuvastatin. Discrete and synergistic effects of the biological activities of Hsp70 may explain its cytoprotective role in obstructive nephropathy. Basic studies point to a combination of effects including inhibition of apoptosis and inflammation, repair of damaged proteins, prevention of unfolded protein aggregation, targeting of damaged protein for degradation, and cytoskeletal stabilization as primary effectors of Hsp70 action. This review summarizes our understanding of how the biological actions of Hsp70 may affect renal cytoprotection in the context of obstructive injury. The potential of Hsp70 to be of central importance to the mechanism of action of various drugs that modify the genesis of experimental obstructive nephropathy is considered.

Heat shock proteins and kidney disease: perspectives of HSP therapy

“…The induction of HO-1/HSP 32 and HSP70 by means of NO-mediated modification in intracellular antioxidants levels is a novel alternative anti-apoptotic mechanism. NO can oxidize intracellular reduced glutathione and thereby change the antioxidant levels within the cell, resulting in oxidative or nitrosative stress (Mazzei et al 2015).…”

Perioperative urinary heat shock protein 72 as an early marker of acute kidney injury in dogs

“…HSPs are abundant cellular proteins that have cellular cytoprotective roles in injury as part of the heat shock response. Their functions include inhibiting apoptosis and inflammation, repairing damage, preventing unfolded protein aggregation, targeting damaged proteins for degradation and stabilizing the cytoskeleton (Mazzei et al 2015). Under stress conditions, HSP transcription and synthesis increase, providing cytoprotection against additional stress (Bruchim et al 2014).…”

Unravelling Pathophysiology of Crystalline Nephropathy in Ceftriaxone-Associated Acute Kidney Injury: A Cellular Proteomic Approach

“…Hsp70 is one of the most highly conserved chaperones, which play crucial roles in kidney diseases, that is, acute kidney injury and obstructive nephropathy [25, 26]. Nevertheless, the roles of Hsp70 in crystalline nephropathy have never been elucidated.…”