Anti-apoptotic effects of arachidonic acid and prostaglandin E2 in pancreatic β-cells
Anti-apoptotic effects of arachidonic acid and prostaglandin E2 in pancreatic β-cells
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DOI：
10.1159/000107544
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发表时间：
2007-01-01
影响因子：
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通讯作者：
Persaud, Shanta J.
中科院分区：
文献类型：
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作者：
Papadimitriou, Alexandros;King, Aileen J. F.;Persaud, Shanta J.
背景/目的：多不饱和脂肪酸花生四烯酸(AA)参与了β细胞防御机制，环氧合酶(COX)2的前列腺素(PG)产物可抵抗四氧嘧啶诱导的胰岛素分泌RIN细胞的凋亡。我们现在已经研究了AA及其代谢物PGE(2)在MIN6小鼠胰岛素分泌β细胞系和小鼠胰岛中的抗凋亡作用。方法：用CAPase-3活性测定方法检测MIN6β细胞和小鼠胰岛提取物的细胞凋亡率，用实时定量RT-PCR方法检测COX2基因的表达水平。结果：AA(3.1-12.5mU M)可诱导MIN6细胞的凋亡率呈浓度依赖性减少，在胞浆磷脂酶A(2)高表达的MIN6细胞中，内源性AA水平升高也得到类似的结果。25 mM葡萄糖可显著上调MIN6细胞COX2基因表达，减少细胞凋亡率。选择性抑制剂NS-398(10-100 mU M)抑制MIN6细胞COX2活性可增加细胞凋亡率，外源性PGE(2)(0.2-5 mU M)可浓度依赖性地抑制NS-398诱导的细胞凋亡。还观察了AA和PGE(2)对原代小鼠胰岛的保护作用。结论：AA及其COX2代谢产物PGE(2)对胰岛β细胞具有保护作用。
Background/ Aims: The polyunsaturated fatty acid arachidonic acid ( AA) has been implicated in beta- cell defence mechanisms and prostaglandin ( PG) products of cyclooxygenase ( COX) 2 action confer resistance to alloxan- induced apoptosis in insulin- secreting RIN cells. We have now investigated the antiapoptotic effects of AA and its metabolite, PGE(2), in the MIN6 mouse insulin- secreting beta-cell line and mouse islets. Methods: Apoptosis was determined in MIN6 beta-cell and mouse islet extracts by measurement of capase- 3 activity, and COX2 mRNA levels were quantified by real- time RT- PCR. Results: Exposure of MIN6 cells to AA ( 3.1- 12.5 mu M) caused concentration-dependent reductions in apoptosis, and similar results were obtained when endogenous AA levels were elevated in cytosolic phospholipase A (2)-overexpressing MIN6 cells. 25mM glucose caused both a significant up- regulation of MIN6 cell COX2 mRNA levels and a decrease in apoptosis. Inhibition of MIN6 cell COX2 activity with a selective inhibitor, NS- 398 ( 10- 100 mu M), increased apoptosis and exogenous PGE(2) ( 0.2- 5 mu M) reduced NS-398- induced apoptosis in a concentration- dependent manner. The protective effects of AA and PGE(2) were also observed in primary mouse islets. Conclusion: These data show that AA and its COX2- generated metabolite, PGE(2), can protect beta-cells from apoptosis.