Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells
- Authors
- Park, Jae Hyeon; Lee, Jeong Eun; Shin, In Chul; Koh, Hyun Chul
- Issue Date
- Apr-2013
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- Chlorpyrifos; Autophagy; Apoptosis; Neuroprotection; Rapamycin; SH-SY5Y cells
- Citation
- TOXICOLOGY AND APPLIED PHARMACOLOGY, v.268, no.1, pp.55 - 67
- Indexed
- SCIE
SCOPUS
- Journal Title
- TOXICOLOGY AND APPLIED PHARMACOLOGY
- Volume
- 268
- Number
- 1
- Start Page
- 55
- End Page
- 67
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/163072
- DOI
- 10.1016/j.taap.2013.01.013
- ISSN
- 0041-008X
- 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.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 의과대학 > 서울 약리학교실 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/163072)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.