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

Autor(es)

Goncalves, Guilherme Lopes ^[1] ; Costa-Pessoa, Juliana Martins ^[1] ; Thieme, Karina ^[1] ; Lins, Bruna Bezerra ^[1] ; Oliveira-Souza, Maria ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Lab Renal Physiol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 8, DEC 20 2018.
• Citações Web of Science: 3

Resumo

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)

• Processo FAPESP: 17/02020-0 - Mecanismos envolvidos na transição da injúria renal aguda pós-isquêmica para a doença renal crônica: contribuição da angiotensina II e da albumina
• Beneficiário: Maria Oliveira de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/17251-9 - Efeitos da administração crônica de albumina modificada por glicação avançada (AGE) sobre o tecido renal: caracterização do perfil inflamatório, antioxidante e epigenético
• Beneficiário: Karina Thieme
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/19569-3 - Efeitos da endotelina 3 e da leptina na morfologia e função renal in vivo: participação do sistema renina-angiotensina intrarrenal
• Beneficiário: Maria Oliveira de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/23087-4 - Estudo molecular e funcional de transportadores de membrana
• Beneficiário: Gerhard Malnic
• Modalidade de apoio: Auxílio à Pesquisa - Temático