https://scholars.lib.ntu.edu.tw/handle/123456789/566115
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Huang, Cheng-Chin | en_US |
dc.contributor.author | CHING-YAO YANG | en_US |
dc.contributor.author | Su, Chin-Chuan | en_US |
dc.contributor.author | Fang, Kai-Min | en_US |
dc.contributor.author | Yen, Cheng-Chieh | en_US |
dc.contributor.author | Lin, Ching-Ting | en_US |
dc.contributor.author | Liu, Jui-Min | en_US |
dc.contributor.author | Lee, Kuan-I | en_US |
dc.contributor.author | Chen, Ya-Wen | en_US |
dc.contributor.author | SHING-HWA LIU | en_US |
dc.contributor.author | Huang, Chun-Fa | en_US |
dc.date.accessioned | 2021-06-23T01:45:22Z | - |
dc.date.available | 2021-06-23T01:45:22Z | - |
dc.date.issued | 2021-04-22 | - |
dc.identifier.issn | 16616596 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/566115 | - |
dc.description.abstract | 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway. | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | International journal of molecular sciences | en_US |
dc.subject | 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP); AMPKα; ER stress; JNK; apoptosis; β-cells | en_US |
dc.title | 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene, a Major Active Metabolite of Bisphenol A, Triggers Pancreatic β-Cell Death via a JNK/AMPKα Activation-Regulated Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.3390/ijms22094379 | - |
dc.identifier.pmid | 33922211 | - |
dc.identifier.scopus | 2-s2.0-85104496265 | - |
dc.identifier.url | https://scholars.lib.ntu.edu.tw/handle/123456789/561661 | - |
dc.relation.journalvolume | 22 | en_US |
dc.relation.journalissue | 9 | en_US |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.languageiso639-1 | en | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.dept | Surgery | - |
crisitem.author.dept | Toxicology | - |
crisitem.author.orcid | 0000-0001-6312-3719 | - |
crisitem.author.orcid | 0000-0002-9976-1197 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
Appears in Collections: | 醫學系 |
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