Restoration of Rab1 Levels Prevents Endoplasmic Reticulum Stress in Hippocampal Cells during Protein Aggregation Triggered by Rotenone

Autor(es)

Lima, Nathan C. R. ^[1] ; Melo, Thaiany Q. ^[1] ; Sakugawa, Andressa Y. S. ^[1] ; Melo, Karla P. ^[1] ; Ferrari, Merari F. R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Rua Matao, 277, Cidade Univ, BR-05508090 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neuroscience; v. 419, p. 5-13, NOV 1 2019.
• Citações Web of Science: 0

Resumo

Disrupted neuronal intracellular trafficking is often related with protein aggregates present in the brain during neurodegenerative diseases such as Alzheimer's. Impairment of intracellular transport may be related to Rab proteins, a class of small GTPases responsible for trafficking of organelles and vesicles. Deficit in trafficking between the endoplasmic reticulum (ER) and Golgi apparatus mediated by Rab1 and 6 may lead to increased unfolded protein response (UPR) and ER stress and remodeling. Thus, the objective of this study is to analyze the levels of Rabs 1 and 6 in the hippocampus of aged rats and in vitro during protein aggregation promoted by exposure to rotenone. Levels of Rabs 1 and 6, ATF6 and CHOP were measured by western blotting. PDI immunolabeling and ER-Tracker were employed to study ER morphology. MTT was used to analyze cell metabolism. Rab1 levels and cell viability decreased, whereas Rab6, UPR proteins and ER remodeling increased during protein aggregation, which were restored to normal levels after exogenous expression of Rab1.These results suggest that decrease of Rab1 levels contributes to ER stress and remodeling, while maintaining the elevated expression of Rab1 prevented impairment of cell viability during protein aggregation. In conclusion, Rab1 is a significant player to maintain intracellular homeostasis and its expression may mitigate ER dysfunction in the context of neurodegeneration-related protein inclusions. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 17/14273-0 - Análise da mitofagia em modelo celular de agregação proteica associada à neurodegeneração
• Beneficiário: Karla Pacheco de Melo
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 15/10892-1 - Estudo dos mecanismos inflamatórios mediados por receptores da imunidade inata na esclerose lateral amiotrófica
• Beneficiário: Renato Barboza
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/06434-7 - Degradação da proteína tau hiperfosforilada e tráfego de organelas durante processos neurodegenerativos associados à agregação protéica em cultura de células do hipocampo
• Beneficiário: Merari de Fátima Ramires Ferrari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/18961-2 - Estudo da autofagia como mecanismo para o desencadeamento de doenças neurodegenerativas
• Beneficiário: Merari de Fátima Ramires Ferrari
• Modalidade de apoio: Auxílio à Pesquisa - Regular