Angiotensin II-induced podocyte apoptosis is media... - BV FAPESP
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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Angiotensin II-induced podocyte apoptosis is mediated by endoplasmic reticulum stress/PKC-delta/p38 MAPK pathway activation and trough increased Na+/H+ exchanger isoform 1 activity

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Author(s):
Cardoso, Vanessa Gerolde [1] ; Goncalves, Guilherme Lopes [1] ; Costa-Pessoa, Juliana Martins [1] ; Thieme, Karina [2] ; Lins, Bruna Bezerra [1] ; Malavazzi Casare, Fernando Augusto [1] ; de Ponte, Mariana Charleaux [1] ; Saraiva Camara, Niels Olsen [3] ; Oliveira-Souza, Maria [1]
Total Authors: 9
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Lab Renal Physiol, BR-05508900 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Med Sch, Lab Carbohydrates & Radioimmunoassays LIM 18, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: BMC Nephrology; v. 19, JUL 13 2018.
Web of Science Citations: 7
Abstract

Background: Angiotensin II (Ang II) contributes to the progression of renal diseases associated with proteinuria and glomerulosclerosis mainly by inducing podocyte apoptosis. In the present study, we investigated whether the chronic effects of Ang II via AT1 receptor (AT1R) would result in endoplasmic reticulum (ER) stress/PKC-delta/p38 MAPK stimulation, and consequently podocyte apoptosis. Methods: Wistar rats were treated with Ang II (200 ng.kg(-1).min(-1), 42 days) and or losartan (10 mg.kg(-1).day(-1), 14 days). Immortalized mouse podocyte were treated with 1 mu M Ang II and/or losartan (1 mu M) or SB203580 (0.1 mu M) (AT1 receptor antagonist and p38 MAPK inhibitor) for 24 h. Kidney sections and cultured podocytes were used to evaluate protein expression by immunofluorescence and immunoblotting. Apoptosis was evaluated by flow cytometry and intracellular pH (pHi) was analyzed using microscopy combined with the fluorescent probe BCECF/AM. Results: Compared with controls, Ang II via AT1R increased chaperone GRP 78/Bip protein expression in rat glomeruli (p < 0.001) as well as in podocyte culture (p < 0.01); increased phosphorylated eIf2-alpha (p < 0.05), PKC-delta (p < 0.01) and p38 MAPK (p < 0.001) protein expression. Furthermore, Ang II induced p38 MAPK-mediated late apoptosis and increased the Bax/Bcl-2 ratio (p < 0.001). Simultaneously, Ang II via AT1R induced p38 MAPK-NHE1-mediated increase of pHi recovery rate after acid loading. Conclusion: Together, our results indicate that Ang II-induced podocyte apoptosis is associated with AT1R/ER stress/PKC-delta/p38 MAPK axis and enhanced NHE1-mediated pHi recovery rate. (AU)

FAPESP's process: 14/19154-0 - Effect of angiotensin II on the cellular mechanisms involved in the podocytes injury
Grantee:Vanessa Gerolde Cardoso
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 13/23087-4 - Molecular and functional study of membrane transporters
Grantee:Gerhard Malnic
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 13/19569-3 - Effects of endothelin-3 and leptin in renal morphology and function in vivo: involvement of the intrarenal renin-angiotensin system
Grantee:Maria Oliveira de Souza
Support Opportunities: Regular Research Grants
FAPESP's process: 11/14022-0 - Effect of interaction between renin-angiotensin-aldosterone system and endothelin 1 and 3 on renal function
Grantee:Fernando Augusto Malavazzi Casare
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 14/17251-9 - The effects of chronic administration of albumin modified by advanced glycation (AGE) on renal tissue: characterization of the inflammatory, antioxidant and epigenetic profile
Grantee:Karina Thieme
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 17/02020-0 - Mechanisms involved in the transition from post-ischemic acute kidney injury to chronic kidney disease: contribution of angiotensin II and albumin
Grantee:Maria Oliveira de Souza
Support Opportunities: Regular Research Grants