Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells
- Title
- Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells
- Author
- 고현철
- Keywords
- Chlorpyrifos; Autophagy; Apoptosis; Neuroprotection; Rapamycin; SH-SY5Y cells
- Issue Date
- 2013-04
- Publisher
- Elsevier Science B.V., Amsterdam
- Citation
- Toxicology And Applied Pharmacology, April 2013, 268(1), P.55-67
- Abstract
- Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including alpha-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF- induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Box and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. Crown Copyright (c) 2013 Published by Elsevier Inc. All rights reserved.
- URI
- https://www.sciencedirect.com/science/article/pii/S0041008X13000343?via%3Dihubhttp://hdl.handle.net/20.500.11754/44317
- ISSN
- 0041-008X
- DOI
- 10.1016/j.taap.2013.01.013
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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