Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 고현철 | - |
dc.date.accessioned | 2017-10-23T01:08:12Z | - |
dc.date.available | 2017-10-23T01:08:12Z | - |
dc.date.issued | 2015-12 | - |
dc.identifier.citation | NEUROTOXICOLOGY, v. 51, Page. 145-157 | en_US |
dc.identifier.issn | 0161-813X | - |
dc.identifier.issn | 1872-9711 | - |
dc.identifier.uri | http://www.sciencedirect.com/science/article/pii/S0161813X15300085?via%3Dihub | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11754/30172 | - |
dc.description.abstract | Recent studies have demonstrated that dynamin-related protein 1 (Drp1), a mitochondrial fission protein, mediates mitochondria-dependent apoptosis through mitochondrial division. However, little is known about the mechanism by which Drp1 modulates apoptosis in response to chlorpyrifos (CPF)-induced toxicity. In this study, we determined that CPF-induced mitochondrial apoptosis is mediated by Drp1 translocation in SH-SY5Y human neuroblastoma cells. Our results showed that CPF treatment induced intrinsic apoptosis by activating caspase-9, caspase-3, and cytochrome c release in SH-SY5Y cells. Cytosolic Drp1 translocated to the mitochondria in CPF-treated cells and was phosphorylated at Ser616. Treating cells with CPF induced the generation of reactive oxygen species (ROS) and activation of mitogen-activated protein kinases (MAPKs). Inhibiting this ROS generation and MAPK activation abolished CPF-induced expression of phospho-Drp1. Furthermore, Drp1 was required for p53 to translocate to the mitochondria under CPF-induced oxidative stress. Treating cells with mitochondrial-division inhibitor-1 (mdivi-1), which blocks Drp1 translocation, increased the viability of CPF-treated cells by abrogating Drp1 translocation and caspase-3 activation. Specifically, pretreating cells with mdivi-1 inhibited Bax translocation to the mitochondria by blocking p53 signaling. Taken together, these data reveal a novel mechanism by which Drp1 activates mitochondrial-dependent apoptosis and indicate that inhibiting Dpr1 function can protect against CPF-induced cytotoxicity. We propose that inhibiting Drp1 is a possible therapeutic approach for pesticide-induced toxicity when hyperactivated Drp1 contributes to pathology. Crown Copyright (C) 2015 Published by Elsevier Inc. All rights reserved. | en_US |
dc.description.sponsorship | This work was supported by the Korea Science and Engineering Foundation (NRF-2008-0062287) through the Medical Research Center at Hanyang University College of Medicine, Republic of Korea, and by a grant ("Effects of pyrethroids pesticide on dopamine nervous system", Project No. PJ010009012015), from the Cooperative Research Program for Agriculture Science & Technology Development, Rural Development Administration, Republic of Korea. | en_US |
dc.language.iso | en | en_US |
dc.publisher | ELSEVIER SCIENCE BV | en_US |
dc.subject | Chlorpyrifos | en_US |
dc.subject | Dynamin-related protein 1 | en_US |
dc.subject | p53 | en_US |
dc.subject | Mitochondrial-division inhibitor-1 | en_US |
dc.subject | Reactive oxidative species | en_US |
dc.subject | Mitogen-activated protein kinase | en_US |
dc.title | Dynamin-related protein 1 mediates mitochondria-dependent apoptosis in chlorpyrifos-treated SH-SY5Y cells | en_US |
dc.type | Article | en_US |
dc.relation.volume | 51 | - |
dc.identifier.doi | 10.1016/j.neuro.2015.10.008 | - |
dc.relation.page | 145-157 | - |
dc.relation.journal | NEUROTOXICOLOGY | - |
dc.contributor.googleauthor | Park, Jae Hyeon | - |
dc.contributor.googleauthor | Ko, Juyeon | - |
dc.contributor.googleauthor | Hwang, Jungwook | - |
dc.contributor.googleauthor | Koh, Hyun Chul | - |
dc.relation.code | 2015001458 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | hckoh | - |
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