Tetraspanin-2 promotes glucotoxic apoptosis by regulating the JNK/-catenin signaling pathway in human pancreatic cells
DC Field | Value | Language |
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dc.contributor.author | Hwang, In-Hu | - |
dc.contributor.author | Park, Junsoo | - |
dc.contributor.author | Kim, Jung Min | - |
dc.contributor.author | Kim, Seung Il | - |
dc.contributor.author | Choi, Jong-Soon | - |
dc.contributor.author | Lee, Kyung-Bok | - |
dc.contributor.author | Yun, Sung Ho | - |
dc.contributor.author | Lee, Min-Goo | - |
dc.contributor.author | Park, Soo Jung | - |
dc.contributor.author | Jang, Ik-Soon | - |
dc.date.accessioned | 2021-09-03T20:25:51Z | - |
dc.date.available | 2021-09-03T20:25:51Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2016-09 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/87630 | - |
dc.description.abstract | Diabetes mellitus is a complex and heterogeneous disease, which has -cell dysfunction at its core. Glucotoxicity affects pancreatic islets, causing -cell apoptosis. However, the role of JNK/-catenin signaling in glucotoxic -cell apoptosis is not well understood. Recently, we identified tetraspanin-2 (TSPAN2) protein as a proapoptotic -cell factor induced by glucose, suggesting that TSPAN2 might contribute to pancreatic -cell glucotoxicity. To investigate the effects of glucose concentration on TSPAN2 expression and apoptosis, we used reverted immortalized RNAKT-15 human pancreatic cells. High TSPAN2 levels up-regulated phosphorylated (p) JNK and induced apoptosis. p-JNK enhanced the phosphorylation of -catenin and Dickkopf-1 (Dkk1). Dkk1 knockdown by small interfering (si)RNA up-regulated nuclear -catenin, suggesting that it is a JNK/-catenin-dependent pathway. siRNA-mediated TSPAN2 depletion in RNAKT-15 cells increased nuclear -catenin. This decreased BCL2-associated X protein (Bax) activation, leading to marked protection against high glucose-induced apoptosis. Bax subfamily proteins induced apoptosis through caspase-3. Thus, TSPAN2 might have induced Bax translocation and caspase-3 activation in pancreatic cells, thereby promoting the apoptosis of RNAKT-15 cells by regulating the JNK/-catenin pathway in response to high glucose concentrations. Targeting TSPAN2 could be a potential therapeutic strategy to treat glucose toxicity-induced -cell failure.Hwang, I.-H., Park, J., Kim, J. M., Kim, S. I., Choi, J.-S., Lee, K.-B., Yun, S. H., Lee, M.-G., Park, S. J., Jang, I.-S. Tetraspanin-2 promotes glucotoxic apoptosis by regulating the JNK/-catenin signaling pathway in human pancreatic cells. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | FEDERATION AMER SOC EXP BIOL | - |
dc.subject | THIOREDOXIN-INTERACTING PROTEIN | - |
dc.subject | WNT | - |
dc.subject | PHOSPHORYLATION | - |
dc.subject | TRANSCRIPTION | - |
dc.subject | GSK3-BETA | - |
dc.subject | MECHANISM | - |
dc.subject | SURVIVAL | - |
dc.subject | BAX | - |
dc.title | Tetraspanin-2 promotes glucotoxic apoptosis by regulating the JNK/-catenin signaling pathway in human pancreatic cells | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Min-Goo | - |
dc.identifier.doi | 10.1096/fj.201600240RR | - |
dc.identifier.scopusid | 2-s2.0-84990852792 | - |
dc.identifier.wosid | 000382816300011 | - |
dc.identifier.bibliographicCitation | FASEB JOURNAL, v.30, no.9, pp.3107 - 3116 | - |
dc.relation.isPartOf | FASEB JOURNAL | - |
dc.citation.title | FASEB JOURNAL | - |
dc.citation.volume | 30 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 3107 | - |
dc.citation.endPage | 3116 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Life Sciences & Biomedicine - Other Topics | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | THIOREDOXIN-INTERACTING PROTEIN | - |
dc.subject.keywordPlus | WNT | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | TRANSCRIPTION | - |
dc.subject.keywordPlus | GSK3-BETA | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | SURVIVAL | - |
dc.subject.keywordPlus | BAX | - |
dc.subject.keywordAuthor | Bax | - |
dc.subject.keywordAuthor | glucose toxicity | - |
dc.subject.keywordAuthor | TSPAN2 | - |
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