Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Jung, Min Jeong | - |
dc.contributor.author | Lee, Jae Meun | - |
dc.contributor.author | Seo, Hye Young | - |
dc.contributor.author | Lim, Ji Sun | - |
dc.contributor.author | Kim, Eun Kyoung | - |
dc.date.available | 2017-07-11T04:43:28Z | - |
dc.date.created | 2017-04-10 | - |
dc.date.issued | 2015-01 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/2611 | - |
dc.description.abstract | Autophagy is a lysosomal degradative pathway that plays an important role in maintaining cellular homeostasis. We previously showed that the inhibition of autophagy causes pancreatic β-cell apoptosis, suggesting that autophagy is a protective mechanism for the survival of pancreatic β-cells. The current study demonstrates that treatment with inhibitors and knockdown of the lysosomal cysteine proteases such as cathepsins B and L impair autophagy, enhancing the caspase-dependent apoptosis of INS-1 cells and islets upon exposure to high concentration of glucose. Interestingly, treatment with cathepsin B and L inhibitors prevented the proteolytic processing of cathepsins B, D and L, as evidenced by gradual accumulation of the respective pro-forms. Of note, inhibition of aspartic cathepsins had no effect on autophagy and cell viability, suggesting the selective role of cathepsins B and L in the regulation of β-cell autophagy and apoptosis. Lysosomal localization of accumulated pro-cathepsins in the presence of cathepsin B and L inhibitors was verified via immunocytochemistry and lysosomal fractionation. Lysotracker staining indicated that cathepsin B and L inhibitors led to the formation of severely enlarged lysosomes in a timedependent manner. The abnormal accumulation of pro-cathepsins following treatment with inhibitors of cathepsins B and L suppressed normal lysosomal degradation and the processing of lysosomal enzymes, leading to lysosomal dysfunction. Collectively, our findings suggest that cathepsin defects following the inhibition of cathepsin B and L result in lysosomal dysfunction and consequent cell death in pancreatic β-cells. Copyright: © 2015 Jung et al. | - |
dc.language | English | - |
dc.publisher | Public Library of Science | - |
dc.title | Cathepsin Inhibition-Induced Lysosomal Dysfunction Enhances Pancreatic Beta-Cell Apoptosis in High Glucose | - |
dc.type | Article | - |
dc.identifier.doi | 10.1371/journal.pone.0116972 | - |
dc.identifier.scopusid | 2-s2.0-84921927022 | - |
dc.identifier.bibliographicCitation | PLoS ONE, v.10, no.1 | - |
dc.description.isOpenAccess | TRUE | - |
dc.subject.keywordPlus | CHRONIC OXIDATIVE STRESS | - |
dc.subject.keywordPlus | ORGANELLAR DYSFUNCTION | - |
dc.subject.keywordPlus | CYSTEINE PROTEASES | - |
dc.subject.keywordPlus | IMPAIRED AUTOPHAGY | - |
dc.subject.keywordPlus | STORAGE DISEASES | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | LC3 | - |
dc.subject.keywordPlus | PATHWAYS | - |
dc.subject.keywordPlus | KINASE | - |
dc.subject.keywordPlus | JNK | - |
dc.citation.number | 1 | - |
dc.citation.title | PLoS ONE | - |
dc.citation.volume | 10 | - |
10.1371_journal.pone.0116972.pdf
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