Akt/GSK3 beta signaling is involved in fipronil-induced apoptotic cell death of human neuroblastoma SH-SY5Y cells
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Jeong Eun | - |
dc.contributor.author | Kang, Jin Sun | - |
dc.contributor.author | Ki, Yeo-Woon | - |
dc.contributor.author | Lee, Sang-Hun | - |
dc.contributor.author | Lee, Soo-Jin | - |
dc.contributor.author | Lee, Kyung Suk | - |
dc.contributor.author | Koh, Hyun Chul | - |
dc.date.accessioned | 2022-07-16T21:17:37Z | - |
dc.date.available | 2022-07-16T21:17:37Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2011-04 | - |
dc.identifier.issn | 0378-4274 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/168764 | - |
dc.description.abstract | Fipronil (FPN) is a phenylpyrazole insecticide acted on insect gamma-aminobutyric acid (GABA) receptors. Although action of FPN is restricted on insect neuronal or muscular transmitter system, a few studies have assessed the effects of this neurotoxicant on neuronal cell death. To determine the mechanisms underlying FPN-induced neuronal cell death, we investigated whether reactive oxygen species (ROS) plays a role in FPN-induced apoptosis, using an in vitro model of human dopaminergic SH-SY5Y cells. FPN was cytotoxic to these cells and its cytotoxicity showed a concentration-dependent manner. Additionally, FPN treatment significantly decreased the tyrosine hydroxylase (TH) expression without change of glutamic acid decarboxylase 65 (GAD65) expression. FPN-induced dopaminergic cell death involved in increase of ROS generation since pretreatment with N-acetyl cysteine (NAC), an anti-oxidant, reduced cell death. After FPN treatment, dopamine (DA) levels decreased significantly in both cell and culture media, and oxidative effects of DA were blocked by NAC pretreatment. We showed that cell death in response to FPN was due to apoptosis since FPN increased cytochrome c release into the cytosol and activated caspase-3. It also led to nuclear accumulation of p53 and reduced the level of Bcl-2 protein in a concentration-dependent manner. Additionally, FPN altered the level of Akt/glycogen synthase kinase-3 (GSK3 beta) phosphorylation. FPN reduced the Akt phosphorylation on Ser473, and in parallel with the inactivation of Akt, phosphorylation of GSK3 beta on Ser9 which inactivates GSK3 beta, decreased after treatment with FPN. Furthermore, inhibition of the GSK3 beta signal protected the cell against FPN-induced cell death. These results suggest that regulation of GSK3 beta activity may control the apoptosis induced by FPN-induced oxidative stress associated with neuronal cell death. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER IRELAND LTD | - |
dc.title | Akt/GSK3 beta signaling is involved in fipronil-induced apoptotic cell death of human neuroblastoma SH-SY5Y cells | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Sang-Hun | - |
dc.contributor.affiliatedAuthor | Lee, Soo-Jin | - |
dc.contributor.affiliatedAuthor | Koh, Hyun Chul | - |
dc.identifier.doi | 10.1016/j.toxlet.2011.01.030 | - |
dc.identifier.scopusid | 2-s2.0-79952627440 | - |
dc.identifier.wosid | 000289708000008 | - |
dc.identifier.bibliographicCitation | TOXICOLOGY LETTERS, v.202, no.2, pp.133 - 141 | - |
dc.relation.isPartOf | TOXICOLOGY LETTERS | - |
dc.citation.title | TOXICOLOGY LETTERS | - |
dc.citation.volume | 202 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 133 | - |
dc.citation.endPage | 141 | - |
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 | Toxicology | - |
dc.relation.journalWebOfScienceCategory | Toxicology | - |
dc.subject.keywordPlus | GLYCOGEN-SYNTHASE KINASE-3-BETA | - |
dc.subject.keywordPlus | PROTEIN-KINASE | - |
dc.subject.keywordPlus | DEVELOPMENTAL NEUROTOXICITY | - |
dc.subject.keywordPlus | NEURONAL APOPTOSIS | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | COMPLEX-I | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | LITHIUM | - |
dc.subject.keywordPlus | BCL-2 | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordAuthor | Fipronil | - |
dc.subject.keywordAuthor | Human dopaminergic neuroblastoma | - |
dc.subject.keywordAuthor | SH-SY5Y cells | - |
dc.subject.keywordAuthor | Apoptosis | - |
dc.subject.keywordAuthor | Reactive oxygen species | - |
dc.subject.keywordAuthor | Akt/GSK3 beta | - |
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.