The Renal Antioxidative Effect of Losartan involves Heat Shock Protein 70(Hsp70) in Proximal Tubule Cells

VALERIA V COSTANTINO; VALERIA CACCIAMANI; VALERIA V COSTANTINO; VALERIA CACCIAMANI; PATRICIA G VALLÉS; ANDREA F GIL LORENZO; PATRICIA G VALLÉS; ANDREA F GIL LORENZO; VICTORIA BOCANEGRA; MARIA EUGENIA BENARDON ; VICTORIA BOCANEGRA; MARIA EUGENIA BENARDON

CELL STRESS & CHAPERONES.

SPRINGER

Año: 2020

1355-8145

Angiotensin II exerts a cardinal role in the pathogenesis of hypertension and renal injury via action of angiotensin II type 1 (AT1) receptors. Local renin-angiotensin system (RAS) activity is essential for the mechanisms mediating athophysiological functions. Proximal tubular angiotensinogen, and tubular AT1 receptors are augmented by intrarenal angiotensin II. Caveolin 1 plays an important role as a regulatory molecule for the compartmentalization of redox signaling events through angiotensin II-induced NADPH oxidase activation in the kidney. A role for the renin-angiotensin system in the development and/or maintenance of hypertension has been demonstrated in spontaneously hypertensive rats (SHR). Many effects of angiotensin II are dependent on the AT1 stimulation of reactive oxygen species (ROS) production by NADPH oxidase. Angiotensin II up-regulation stimulates oxidative stress in proximal tubules from SHR. The NADPH oxidase 4 (Nox4) is abundantly expressed in kidney proximal tubule cells. Induction of the stress response includes synthesis of heat shock protein 70, a molecular chaperone that has a critical role in the recovery of cells from stress and in cytoprotection, guarding cells from subsequent insults. HSP70 chaperones function, in part by driving the molecular triage decision, which determines whether proteins enter the productive folding pathway or result in client substrate ubiquitination and proteasomal degradation.This review examines regulation of Losartan-mediated antioxidative stress responses by the chaperone HSP70 in proximal tubule cellsof spontaneously hypertensive rats.