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Protective role of autophagy in palmitate-induced INS-1 beta-cell death.

Authors
Choi, SE; Lee, SM; Lee, YJ; Li, LJ; Lee, SJ; Lee, JH; Kim, Y; Jun, HS; Lee, KW; Kang, Y
Citation
Endocrinology, 150(1):126-134, 2009
Journal Title
Endocrinology
ISSN
0013-72271945-7170
Abstract
Autophagy, a vacuolar degradative pathway, constitutes a stress adaptation that avoids cell death or elicits the alternative cell-death pathway. This study was undertaken to determine whether autophagy is activated in palmitate (PA)-treated beta-cells and, if activated, what the role of autophagy is in the PA-induced beta-cell death. The enhanced formation of autophagosomes and autolysosomes was observed by exposure of INS-1 beta-cells to 400 microm PA in the presence of 25 mm glucose for 12 h. The formation of green fluorescent protein-LC3-labeled structures (green fluorescent protein-LC3 dots), with the conversion from LC3-I to LC3-II, was also distinct in the PA-treated cells. The phospho-mammalian target of rapamycin level, a typical signal pathway that inhibits activation of autophagy, was gradually decreased by PA treatment. Blockage of the mammalian target of rapamycin signaling pathway by treatment with rapamycin augmented the formation of autophagosomes but reduced PA-induced INS-1 cell death. In contrast, reduction of autophagosome formation by knocking down the ATG5, inhibition of fusion between autophagosome and lysosome by treatment with bafilomycin A1, or inhibition of proteolytic degradation by treatment with E64d/pepstatin A, significantly augmented PA-induced INS-1 cell death. These findings showed that the autophagy system could be activated in PA-treated INS-1 beta-cells, and suggested that the induction of autophagy might play an adaptive and protective role in PA-induced cell death.
MeSH terms
AnimalsAutophagy*/drug effectsCaspase 3/drug effectsCaspase 3/metabolismCell Death/drug effects*Cell Nucleus/drug effectsCell Nucleus/pathologyCell Survival/drug effectsGlucose/pharmacologyInsulin-Secreting Cells/drug effectsInsulin-Secreting Cells/pathology*Insulinoma/pathologyPalmitic Acid/pharmacology*Pancreatic Neoplasms/geneticsPancreatic Neoplasms/pathologyRNA InterferenceRatsSignal Transduction/drug effects
DOI
10.1210/en.2008-0483
PMID
18772242
Appears in Collections:
Journal Papers > Research Organization > Chronic Inflammatory Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
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