Protective Role of Autophagy in Palmitate-Induced INS-1 β-Cell Death

Endocrinology - Tập 150 Số 1 - Trang 126-134 - 2009
Sung-E Choi1, Sung-Mi Lee1, Youn-Jung Lee1, Ling-Ji Li1, Soo‐Jin Lee1, Ji‐Hyun Lee1, Youngsoo Kim2, Hee‐Sook Jun3, Kwan Woo Lee4, Yup Kang1
1Institute for Medical Science (S.-E.C., S.-M.L., Y.-J.L., L.-J.L., S.-J.L., J.-H.L., Y.K.), Ajou University School of Medicine, Suwon 442-749, Republic of Korea
2Cancer Research Institute (Y.K.), College of Medicine, Seoul National University, Seoul 110-749, Republic of Korea
3Leegilya Cancer and Diabetes Institute (H.-S.J.), Gachon University of Medicine and Science, Inchon 406-799, Republic of Korea
4Department of Endocrinology and Metabolism (K.-W.L.), Ajou University School of Medicine, Suwon 442-749, Republic of Korea

Tóm tắt

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 β-cells and, if activated, what the role of autophagy is in the PA-induced β-cell death. The enhanced formation of autophagosomes and autolysosomes was observed by exposure of INS-1 β-cells to 400 μm 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 β-cells, and suggested that the induction of autophagy might play an adaptive and protective role in PA-induced cell death. Autophagy is activated in palmitate-treated insulinoma-1 beta cells, and the induction of autophagy plays a protective role in palmitate-induced beta cell death.

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Endocrinology

Tập 150 Số 1

126-134

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