Hypoxia-induced neuronal apoptosis is mediated by de novo synthesis of ceramide through activation of serine palmitoyltransferase
DC Field | Value | Language |
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dc.contributor.author | Kang, Mi Sun | - |
dc.contributor.author | Ahn, Kyong Hoon | - |
dc.contributor.author | Kim, Seok Kyun | - |
dc.contributor.author | Jeon, Hyung Jun | - |
dc.contributor.author | Ji, Jung Eun | - |
dc.contributor.author | Choi, Jong Min | - |
dc.contributor.author | Jung, Kwang Mook | - |
dc.contributor.author | Jung, Sung Yun | - |
dc.contributor.author | Kim, Dae Kyong | - |
dc.date.available | 2019-05-30T01:39:36Z | - |
dc.date.issued | 2010-04 | - |
dc.identifier.issn | 0898-6568 | - |
dc.identifier.issn | 1873-3913 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/22552 | - |
dc.description.abstract | Cellular hypoxia can lead to cell death or adaptation and has important effects on development, physiology, and pathology. Here, we investigated the role and regulation of ceramide in hypoxia-induced apoptosis of SH-SY5Y neuroblastoma cells. Hypoxia increased the ceramide concentration; subsequently, we observed biochemical changes indicative of apoptosis, such as DNA fragmentation, nuclear staining, and poly ADPribose polymerase (PARP) cleavage. The hypoxic cell death was potently inhibited by a caspase inhibitor, zVAD-fmk (benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone). L-Cycloserine, a serine palmitoyltransferase (SPT) inhibitor, and fumonisin B, (FBI), a ceramide synthase inhibitor, inhibited the hypoxia-induced increase in ceramide, indicating that the increase occurred via the de novo pathway. Hypoxia increased the activity and protein levels of SPT2, suggesting that the hypoxia-induced increase in ceramide is due to the transcriptional up-regulation of SPT2. Specific siRNA of SPT2 prevented hypoxia-induced cell death and ceramide production. However, hypoxia also increased the cellular level of glucosylceramide, which was inhibited by a glucosylceramide synthase (GCS) inhibitor and specific siRNA, but not a ceramidase inhibitor. The increase in glucosylceramide was accompanied by increases in both PARP cleavage and DNA fragmentation. Together. the current results suggest that both SPT and GCS may regulate the cellular level of ceramide, and thus may be critical enzymes for deciding the fate of the cells exposed to hypoxia. (C) 2009 Elsevier Inc. All rights reserved. | - |
dc.format.extent | 9 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | ELSEVIER SCIENCE INC | - |
dc.title | Hypoxia-induced neuronal apoptosis is mediated by de novo synthesis of ceramide through activation of serine palmitoyltransferase | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.cellsig.2009.11.015 | - |
dc.identifier.bibliographicCitation | CELLULAR SIGNALLING, v.22, no.4, pp 610 - 618 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000275149300006 | - |
dc.identifier.scopusid | 2-s2.0-74449084424 | - |
dc.citation.endPage | 618 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 610 | - |
dc.citation.title | CELLULAR SIGNALLING | - |
dc.citation.volume | 22 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordAuthor | Hypoxia | - |
dc.subject.keywordAuthor | Ceramide | - |
dc.subject.keywordAuthor | Serine palmitoytransferase | - |
dc.subject.keywordAuthor | Glucosylceramide synthase | - |
dc.subject.keywordAuthor | Ceramidase | - |
dc.subject.keywordAuthor | Apoptosis | - |
dc.subject.keywordPlus | TUMOR-NECROSIS-FACTOR | - |
dc.subject.keywordPlus | DAUNORUBICIN-INDUCED APOPTOSIS | - |
dc.subject.keywordPlus | CULTURED HUMAN KERATINOCYTES | - |
dc.subject.keywordPlus | INDUCED CELL-DEATH | - |
dc.subject.keywordPlus | GLUCOSYLCERAMIDE SYNTHASE | - |
dc.subject.keywordPlus | NEUTRAL SPHINGOMYELINASE | - |
dc.subject.keywordPlus | CANCER-CELLS | - |
dc.subject.keywordPlus | FACTOR-ALPHA | - |
dc.subject.keywordPlus | GLYCOSPHINGOLIPID METABOLISM | - |
dc.subject.keywordPlus | INDUCED CYTOTOXICITY | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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