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- Title
The renal antioxidative effect of losartan involves heat shock protein 70 in proximal tubule cells.
- Authors
Vallés, Patricia G.; Bocanegra, Victoria; Costantino, Valeria V.; Gil Lorenzo, Andrea F.; Benardon, María Eugenia; Cacciamani, Valeria
- 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.
- Subjects
PROXIMAL kidney tubules; REACTIVE oxygen species; RENIN-angiotensin system; HEAT shock proteins; ANGIOTENSIN II; NADPH oxidase; MOLECULAR chaperones; PATHOLOGY
- Publication
Cell Stress & Chaperones, 2020, Vol 25, Issue 5, p753
- ISSN
1355-8145
- Publication type
Article
- DOI
10.1007/s12192-020-01119-8