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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.)

Intracellular albumin overload elicits endoplasmic reticulum stress and PKC-delta/p38 MAPK pathway activation to induce podocyte apoptosis

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Goncalves, Guilherme Lopes [1] ; Costa-Pessoa, Juliana Martins [1] ; Thieme, Karina [1] ; Lins, Bruna Bezerra [1] ; Oliveira-Souza, Maria [1]
Total Authors: 5
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Lab Renal Physiol, Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 8, DEC 20 2018.
Web of Science Citations: 3

Podocyte injury is closely related to proteinuria and the progression of chronic kidney disease (CKD). Currently, there is no conclusive understanding about the mechanisms involved in albumin overload and podocyte apoptosis response. In this study, we sought to explore the ways by which intracellular albumin can mediate podocyte apoptosis. Here, immortalized mouse podocytes were treated with bovine serum albumin (BSA) at different times and concentrations, in the presence or absence of SB203580 (0.1 mu M, inhibitor of mitogen-activated-protein kinase -p38MAPK). Using immunofluorescence images, flow cytometry and immunoblotting, we observed a time-dependent intracellular accumulation of fluorescent albumin-FITC-BSA, followed by concentration-and time-dependent effect of intracellular albumin overload on podocyte apoptosis, which was mediated by increased expression of the chaperone glucose-regulated-protein 78 (GRP 78) and phosphorylated inositol-requiring enzyme 1 alpha (pIRE1-alpha), as well as protein kinase C delta (PKC-delta), p38MAPK and cleaved caspase 12 expression. SB203580 prevented the cleavage of caspase 12 and the albumin-mediated podocyte apoptosis. These results suggest that intracellular albumin overload is associated with endoplasmic reticulum (ER) stress and upregulation of PKC-delta/p38MAPK/caspase 12 pathway, which may be a target for future therapeutic of albumin-induced podocyte apoptosis. (AU)

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 type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/23087-4 - Molecular and functional study of membrane transporters
Grantee:Gerhard Malnic
Support type: Research Projects - Thematic Grants
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 type: Regular Research 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 type: Regular Research Grants