Potential autophagy enhancers protect against fipronil-induced apoptosis in SH-SY5Y cells

Title
Potential autophagy enhancers protect against fipronil-induced apoptosis in SH-SY5Y cells
Author
고현철
Keywords
Fipronil; Autophagy; Apoptosis; Neuroprotection; Rapamycin; Reactive oxygen species; OXIDATIVE STRESS; PARKINSONS-DISEASE; IN-VITRO; DEATH; RAPAMYCIN; CHLORPYRIFOS; NEURODEGENERATION; INHIBITION; CYTOTOXICITY; ACTIVATION
Issue Date
2013-10
Publisher
Elsevier Science B.V., Amsterdam.
Citation
Toxicology Letters, 2013, 223(1), P.25-34
Abstract
Oxidative stress created by environmental toxicants activates several signaling pathways. Autophagy is one of the first lines of defense against oxidative stress damage. The autophagy pathway can be induced and up-regulated in response to intracellular reactive oxygen species (ROS). Recently, we reported that fipronil (FPN)-induced mitochondria-dependent apoptosis is mediated through ROS in human neuroblastoma SH-SY5Y cells. In this study, we explored the role of autophagy to prevent FPN neurotoxicity. We investigated the modulation of FPN-induced apoptosis according to autophagy regulation. FPN activated caspase-9 and caspase-3, and induced nuclear fragmentation and condensation, all of which indicate that FPN-induced cell death was due to apoptosis. In addition, we observed FPN-induced autophagic cell death by monitoring the expression of LC3-II and Beclin-1. Exposure to FPN in SH-SY5Y cells led to the production of ROS. Treatment with N-acetyl-cysteine (NAC) effectively blocked both apoptosis and autophagy. Interestingly, pretreatment with rapamycin, an autophagy inducer, significantly enhanced the viability of FPN-exposed cells; the enhancement of cell viability was partially due to alleviation of FPN-induced apoptosis via a decrease in levels of cleaved caspase-3. However, pretreatment with 3-methyladenine (3MA) a specific inhibitor for autophagy, remarkably strengthened FPN toxicity and further induced activation of caspase-3 in these cells. Our studies suggest that FPN-induced cytotoxicity is modified by autophagy regulation and that rapamycin is neuroprotective against FPN-induced apoptosis through enhancing autophagy. Crown Copyright (C) 2013 Published by Elsevier Ireland Ltd. All rights reserved.
URI
https://ac.els-cdn.com/S0378427413012873/1-s2.0-S0378427413012873-main.pdf?_tid=e702a3a5-5da3-496a-9f9e-10afa30180cd&acdnat=1520508092_88401c8c438083bd5e58b5b3f2f1f8cchttp://hdl.handle.net/20.500.11754/44436
ISSN
0378-4274
DOI
10.1016/j.toxlet.2013.08.015
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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