PrPC displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrPC knockout mice

Autor(es)

Bertuchi, Fernanda R. ^[1] ; Bourgeon, Dominique M. G. ^[2] ; Landemberger, Michele C. ^[2] ; Martins, Vilma R. ^[2] ; Cerchiaro, Giselle ^[1]

Afiliação do(s) autor(es)

^[1] Fed Univ ABC UFABC, Ctr Nat Sci & Humanities, BR-09210170 Santo Andre, SP - Brazil

^[2] AC Camargo Hosp, Int Ctr Res & Educ, BR-01505010 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Biochemical and Biophysical Research Communications; v. 418, n. 1, p. 27-32, FEB 3 2012.
• Citações Web of Science: 22

Resumo

The PrPC protein, which is especially present in the cellular membrane of nervous system cells, has been extensively studied for its controversial antioxidant activity. In this study, we elucidated the free radical scavenger activity of purified murine PrPc in solution and its participation as a cell protector in astrocytes that were subjected to treatment with an oxidant. In vitro and using an EPR spin-trapping technique, we observed that PrPC decreased the oxidation of the DMPO trap in a Fenton reaction system (Cu2+/ascorbate/H2O2), which was demonstrated by approximately 70% less DMPO/OH. In cultured PrPC-knockout astrocytes from mice, the absence of PrPC caused an increase in intracellular ROS (reactive oxygen species) generation during the first 3 h of H2O2 treatment. This rapid increase in ROS disrupted the cell cycle in the PrPC-knockout astrocytes, which increased the population of cells in the sub-G1 phase when compared with cultured wild-type astrocytes. We conclude that PrPC in solution acts as a radical scavenger, and in astrocytes, it is essential for protection from oxidative stress caused by an external chemical agent, which is a likely condition in human neurodegenerative CNS disorders and pathological conditions such as ischemia. (C) 2011 Elsevier inc. All rights reserved. (AU)

• Processo FAPESP: 07/50765-2 - Estudo de processos oxidativos e radicalares envolvendo o cobre no meio biológico: uma investigação de mecanismos moleculares da atividade oxidante de complexos e proteínas contendo cobre
• Beneficiário: Giselle Cerchiaro
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 09/14027-2 - Mecanismos associados à função da proteína prion e seu ligante STI1/Hop: abordagens terapêuticas
• Beneficiário: Vilma Regina Martins
• Modalidade de apoio: Auxílio à Pesquisa - Temático