The renal antioxidative effect of losartan involves heat shock protein 70 in proximal tubule cells
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MINI REVIEW
The renal antioxidative effect of losartan involves heat shock protein 70 in proximal tubule cells Patricia G. Vallés 1,2 & Victoria Bocanegra 2 & Valeria V. Costantino 2 & Andrea F. Gil Lorenzo 1 & María Eugenia Benardon 1 & Valeria Cacciamani 2 Received: 23 December 2019 / Revised: 30 April 2020 / Accepted: 6 May 2020 # Cell Stress Society International 2020
Abstract 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 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 (SHRs). Many effects of angiotensin II are dependent on the AT1 stimulation of reactive oxygen species (ROS) production by NADPH oxidase. Angiotensin II upregulation 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 cells of spontaneously hypertensive rats. Keywords Heat shock proteins 70 (HSP70) . Renal proximal tubule cells . Angiotensin II . Losartan . Nox4 NADPH oxidase
Introduction The underlying pathogenesis of hypertension and renal injury occurs substantially as a result of inappropriate activation of cellular processes downstream of the interaction of angiotensin II with its cognate receptor, AT1 (Navar et al. 2002). Activity of local renin-angiotensin system (RAS) is essential for the mechanisms mediating pathophysiological functions of the diseases considered. In particular, the angiotensin II content of renal tissues may be significantly higher in persons afflicted with certain diseases that can be explained on the basis of equilibration with * Patricia G. Vallés [email protected] 1
Área de Fisiopatología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
2
IMBECU CONICET (National Council of Scientific and Technical Research of Argentina), Mendoza, Argentina
the circulating concentrations of this peptide hormone (Navar
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