Fatty acid protection from palmitic acid-induced apoptosis is lost following PI3-kinase inhibition
Fatty acid protection from palmitic acid-induced apoptosis is lost following PI3-kinase inhibition
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DOI：
10.1023/b:appt.0000038039.82506.0c
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发表时间：
2004-09-01
期刊：
影响因子：
7.2
通讯作者：
Green, IC
中科院分区：
文献类型：
--
作者：
Beeharry, N;Chambers, JA;Green, IC
我们之前已经证明，饱和脂肪酸会诱导 DNA 损伤，并导致产生胰岛素的 β 细胞凋亡。在这里，我们进一步研究单一或组合膳食脂肪酸对 RINm5F 存活或细胞死亡信号传导的影响。棕榈酸酯和硬脂酸酯，但不包括亚油酸酯、油酸酯或棕榈酰甲酯，在暴露 24 小时后，会诱导 RINm5F 细胞生长抑制并增加细胞凋亡。与神经酰胺合成抑制剂、多球壳菌素或伏马菌素 B-1 共孵育并不能提高棕榈酸处理的 RINm5F 细胞的活力。诱导型一氧化氮合酶抑制剂 1400 W 同样没有保护作用。然而，亚油酸可以防止棕榈酸诱导的细胞凋亡和坏死性细胞死亡。磷脂酰肌醇3-激酶的特异性药理学抑制剂LY294002和渥曼青霉素消除了亚油酸对细胞凋亡的保护作用，但对坏死没有作用。这些数据表明，饱和脂肪酸棕榈酸酯对RINm5F细胞的生长抑制和细胞凋亡诱导作用通过与多不饱和脂肪酸亚油酸酯共孵育而被阻止，而不是与神经酰胺或一氧化氮生成抑制剂共孵育。磷脂酰肌醇 3-激酶在介导细胞凋亡中亚油酸减少中发挥着关键作用。
We have previously shown that saturated fatty acids induce DNA damage and cause apoptotic cell death in insulin-producing beta-cells. Here we examine further the effects of single or combined dietary fatty acids on RINm5F survival or cell death signalling. Palmitate and stearate, but not linoleate, oleate or palmitoylmethyl ester, induced growth inhibition and increased apoptosis in RINm5F cells following 24 h exposure. Co-incubation with inhibitors of ceramide synthesis, myriocin or fumonisin B-1, did not improve viability of palmitic acid treated RINm5F cells. The inhibitor of inducible nitric oxide synthase, 1400 W, similarly had no protective effect. However, linoleic acid protected against palmitic acid-induced apoptotic and necrotic cell death. The specific pharmacological inhibitors of phosphatidylinositol 3-kinase, LY294002 and wortmannin, abolished the protective effect of linoleic acid on apoptosis but not on necrosis. These data show that the growth inhibitory and apoptosis-inducing effect of the saturated fatty acid palmitate on RINm5F cells is prevented by co-incubation with the polyunsaturated fatty acid linoleate but not inhibitors of ceramide or nitric oxide generation. A key role for phosphatidylinositol 3-kinase in mediating the linoleic-acid reduction in apoptosis is suggested.