NF-κB/mTOR-mediated autophagy can regulate diquat-induced apoptosis
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Aeri | - |
dc.contributor.author | Koh, Hyun Chul | - |
dc.date.accessioned | 2022-07-09T15:06:23Z | - |
dc.date.available | 2022-07-09T15:06:23Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2019-05 | - |
dc.identifier.issn | 0340-5761 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/147880 | - |
dc.description.abstract | Autophagy and apoptosis are the major types of cell death in pesticide-induced neurotoxicity, and autophagy is known to play a role in cell protection by inhibiting apoptosis. In this study, we characterized the relationship between autophagy and apoptosis in diquat (DQ)-induced cell death and explored a novel pharmacotherapeutic approach involving autophagy regulation to prevent DQ neurotoxicity. DQ was cytotoxic to PC12 cells in a concentration-dependent manner, as shown by decreased cell viability and decreased dopamine (DA) levels. DQ-induced apoptosis was found in PC12 cells, as demonstrated by activation of caspase-3 and -9 and by nuclear condensation. By monitoring expression of microtubule-associated protein 1A/1B light chain 3B (LC3-II) and p62, DQ was found to induce autophagy. Exposure of PC12 cells to DQ led to the production of reactive oxygen species (ROS), and N-acetyl-cysteine (NAC) antioxidant effectively blocked both apoptosis and autophagy. Interestingly, DQ in PC12 cells showed increased p53 and NF-kappa B in a time-dependent manner; furthermore, pifithrin-alpha (PFT-alpha), a p53 inhibitor, downregulates the cytotoxicity of DQ, as shown by decreased LC3-II and cleaved caspase-3. SN50, an NF-kappa B inhibitor, results in diminished LC3-II, cleaved caspase-3, and p53. DQ induces mitogen-activated protein kinase (MAPK) signaling including ERK, JNK, and p38, which inhibit regulated apoptosis and autophagic cell death by controlling mTOR signaling. In addition, modulation of DQ-induced apoptosis in response to autophagy regulation was investigated. Pretreatment with rapamycin, an autophagy inducer, significantly enhanced the viability of DQ-exposed cells by alleviating DQ-induced apoptosis. Conversely, cell pretreatment with 3-methyladenine (3MA), an autophagy inhibitor increased DQ toxicity. Our results suggest that DQ-induced cytotoxicity is modified by autophagy regulation. Pharmacologic induction of autophagy may be a useful treatment strategy in neurodegenerative disorders. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | SPRINGER HEIDELBERG | - |
dc.title | NF-κB/mTOR-mediated autophagy can regulate diquat-induced apoptosis | - |
dc.title.alternative | NF-kappa B/mTOR-mediated autophagy can regulate diquat-induced apoptosis | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Koh, Hyun Chul | - |
dc.identifier.doi | 10.1007/s00204-019-02424-7 | - |
dc.identifier.scopusid | 2-s2.0-85062707662 | - |
dc.identifier.wosid | 000469762400006 | - |
dc.identifier.bibliographicCitation | ARCHIVES OF TOXICOLOGY, v.93, no.5, pp.1239 - 1253 | - |
dc.relation.isPartOf | ARCHIVES OF TOXICOLOGY | - |
dc.citation.title | ARCHIVES OF TOXICOLOGY | - |
dc.citation.volume | 93 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 1239 | - |
dc.citation.endPage | 1253 | - |
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 | CHLORPYRIFOS-INDUCED APOPTOSIS | - |
dc.subject.keywordPlus | INDUCED CELL-DEATH | - |
dc.subject.keywordPlus | INDUCTION CONTRIBUTES | - |
dc.subject.keywordPlus | SIGNALING PATHWAYS | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | JNK | - |
dc.subject.keywordPlus | ERK | - |
dc.subject.keywordPlus | DEGENERATION | - |
dc.subject.keywordAuthor | Diquat (DQ) | - |
dc.subject.keywordAuthor | Autophagy | - |
dc.subject.keywordAuthor | Apoptosis | - |
dc.subject.keywordAuthor | P53 | - |
dc.subject.keywordAuthor | NF-kappa B | - |
dc.subject.keywordAuthor | mTOR | - |
dc.subject.keywordAuthor | MAPKs | - |
dc.identifier.url | https://link.springer.com/article/10.1007%2Fs00204-019-02424-7 | - |
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