Dynamin-related protein 1 mediates mitochondria-dependent apoptosis in chlorpyrifos-treated SH-SY5Y cells
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Jae Hyeon | - |
dc.contributor.author | Ko, Juyeon | - |
dc.contributor.author | Hwang, Jungwook | - |
dc.contributor.author | Koh, Hyun Chul | - |
dc.date.accessioned | 2022-07-15T20:00:13Z | - |
dc.date.available | 2022-07-15T20:00:13Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2015-12 | - |
dc.identifier.issn | 0161-813X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/155725 | - |
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. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.title | Dynamin-related protein 1 mediates mitochondria-dependent apoptosis in chlorpyrifos-treated SH-SY5Y cells | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Hwang, Jungwook | - |
dc.contributor.affiliatedAuthor | Koh, Hyun Chul | - |
dc.identifier.doi | 10.1016/j.neuro.2015.10.008 | - |
dc.identifier.scopusid | 2-s2.0-84945567484 | - |
dc.identifier.wosid | 000366953900015 | - |
dc.identifier.bibliographicCitation | NEUROTOXICOLOGY, v.51, pp.145 - 157 | - |
dc.relation.isPartOf | NEUROTOXICOLOGY | - |
dc.citation.title | NEUROTOXICOLOGY | - |
dc.citation.volume | 51 | - |
dc.citation.startPage | 145 | - |
dc.citation.endPage | 157 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalResearchArea | Toxicology | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Toxicology | - |
dc.subject.keywordPlus | GTPASE EFFECTOR DOMAIN | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | DEVELOPMENTAL NEUROTOXICITY | - |
dc.subject.keywordPlus | DIFFERENTIAL MODULATION | - |
dc.subject.keywordPlus | SELECTIVE INHIBITOR | - |
dc.subject.keywordPlus | PARKINSONS-DISEASE | - |
dc.subject.keywordPlus | KINASE PATHWAYS | - |
dc.subject.keywordPlus | DNA-DAMAGE | - |
dc.subject.keywordPlus | PC12 CELLS | - |
dc.subject.keywordAuthor | Chlorpyrifos | - |
dc.subject.keywordAuthor | Dynamin-related protein 1 | - |
dc.subject.keywordAuthor | p53 | - |
dc.subject.keywordAuthor | Mitochondrial-division inhibitor-1 | - |
dc.subject.keywordAuthor | Reactive oxidative species | - |
dc.subject.keywordAuthor | Mitogen-activated protein kinase | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0161813X15300085?via%3Dihub | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Korea+82-2-2220-1365
COPYRIGHT © 2021 HANYANG UNIVERSITY.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.