The renal antioxidative effect of losartan involves heat shock protein 70 in proximal tubule cells

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

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 pathophysiological functions.Proximal tubular angiotensinogen and tubular AT1 receptors are augmented by intrarenal angiotensin II. Caveolin 1 plays animportant role as a regulatory molecule for the compartmentalization of redox signaling events through angiotensin II?inducedNADPH oxidase activation in the kidney. A role for the renin-angiotensin system in the development and/or maintenance ofhypertension has been demonstrated in spontaneously hypertensive rats (SHRs). Many effects of angiotensin II are dependent onthe AT1 stimulation of reactive oxygen species (ROS) production by NADPH oxidase. Angiotensin II upregulation stimulatesoxidative stress in proximal tubules from SHR. The NADPH oxidase 4 (Nox4) is abundantly expressed in kidney proximaltubule cells. Induction of the stress response includes synthesis of heat shock protein 70, a molecular chaperone that has a criticalrole in the recovery of cells from stress and in cytoprotection, guarding cells from subsequent insults. HSP70 chaperones functionin part by driving the molecular triage decision, which determines whether proteins enter the productive folding pathway or resultin client substrate ubiquitination and proteasomal degradation. This review examines regulation of losartan-mediated antioxidative stress responses by the chaperone HSP70 in proximal tubule cells of spontaneously hypertensive rats