Open AccessThe renal antioxidative effect of losartan involves heat shock protein 70 in proximal tubule cells
Author(s) -
Patricia G. Vallés,
Victoria Bocanegra,
Valeria Victoria Costantino,
Andrea Fernanda Gil Lorenzo,
María Eugenia Benardón,
Valeria Cacciamani
Publication year - 2020
Publication title -
cell stress and chaperones
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.994
H-Index - 87
eISSN - 1466-1268
pISSN - 1355-8145
DOI - 10.1007/s12192-020-01119-8
Subject(s) - angiotensin ii , nox4 , nadph oxidase , angiotensin ii receptor type 1 , losartan , renin–angiotensin system , microbiology and biotechnology , oxidative stress , chemistry , medicine , endocrinology , receptor , biology , biochemistry , blood pressure
Angiotensin II exerts a cardinal role in the pathogenesis of hypertension and renal injury via action of angiotensin II type 1 (AT 1 ) receptors. Local renin-angiotensin system (RAS) activity is essential for the mechanisms mediating pathophysiological functions. Proximal tubular angiotensinogen and tubular AT 1 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 AT 1 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.