Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2 |
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Authors: | Dr H Iwahashi T Hanafusa Y Eguchi H Nakajima J Miyagawa N Itoh K Tomita M Namba M Kuwajima T Noguchi Y Tsujimoto Y Matsuzawa |
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Institution: | (1) Second Department of Internal Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, 565 Osaka, Japan;(2) Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Osaka, Japan;(3) Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Osaka, Japan;(4) Department of Laboratory Medicine, School of Medicine, University of Tokushima, Tokushima, Japan;(5) Department of Biochemistry, Fukui Medical School, Fukui, Japan |
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Abstract: | Summary Cytokines are thought to contribute to the induction of pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. The molecular mechanisms that underlie beta-cell death were investigated by studying cytokine-induced cell death in beta-cell lines. A combination of three cytokines (interleukin-1, tumour necrosis factor-, and interferon-) induced apoptotic cell death in the mouse pancreatic beta-cell line TC1, as judged from the appearance of cells with hypodiploid nuclei and oligonucleosomal DNA fragmentation. The same treatment also induced apoptosis in the mouse pancreatic alpha-cell line TC1 and the NOD/Lt mouse beta-cell line NIT-1, although to a lesser extent than in TC1 cells. The abundance of endogenous Bcl-2 in TC1 cells was lower than that in the other two cell lines. Overexpression of human Bcl-2 in TC1 cells partially protected them from cytokine-induced cell death. These results suggest that apoptosis may be responsible, at least in part, for cytokine-induced beta-cell destruction and that Bcl-2 prevents apoptosis in pancreatic islet cells.Abbreviations IDDM
Insulin-dependent diabetes mellitus
- IL
interleukin
- TNF
tumour necrosis factor
- IFN
interferon
- FBS
fetal bovine serum
- ATA
aurintricarboxylic acid
- CHX
cycloheximide
- PI
propidium iodide |
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Keywords: | Pancreatic beta cell Bcl-2 apoptosis cytokine interleukin-1 tumour necrosis factor interferon-" target="_blank">gif" alt="gamma" align="MIDDLE" BORDER="0"> |
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