de Pablo M A, Susin S A, Jacotot E, Larochette N, Costantini P, Ravagnan L, Zamzami N, Kroemer G
Centre National de la Recherche Scientifique, Unité Propre de Recherche 420, 19 rue Guy Môquet, F-94801 Villejuif, France.
Apoptosis. 1999 Apr;4(2):81-7. doi: 10.1023/a:1009694124241.
The fatty acid palmitate can induce apoptosis. Here we show that the palmitate-induced dissipation of the mitochondrial transmembrane potential (Delta Psi m), which precedes nuclear apoptosis, is not prevented by inhibitors of mRNA synthesis, protein synthesis, caspases, or pro-apoptotic ceramide signaling. However, the mitochondrial and nuclear effects of palmitate are inhibited by overexpression of anti-apoptotic proto-oncogene product Bcl-2 and exacerbated by 2-bromo-palmitate as well as by carnitine. The cytoprotective actions of Bcl-2, respectively, is not antagonized by etomoxir, an inhibitor of carnitine palmitoyl transferase 1 (CPT1), suggesting that the recently described physical interaction between CPT1 and Bcl-2 is irrelevant to Bcl-2-mediated inhibition of palmitate-induce apoptosis. When added to purified mitochondria, palmitate causes the release of soluble factors capable of stimulating the apoptosis of isolated nuclei in a cell-free system. Mitochondria purified from Bcl-2 over-expressing cells are protected against the palmitate-stimulated release of such factors. These data suggest that palmitate causes apoptosis via a direct effect on mitochondria.
脂肪酸棕榈酸盐可诱导细胞凋亡。在此我们表明，棕榈酸盐诱导的线粒体跨膜电位（ΔΨm）耗散先于细胞核凋亡，且不受mRNA合成抑制剂、蛋白质合成抑制剂、半胱天冬酶或促凋亡神经酰胺信号传导抑制剂的阻止。然而，棕榈酸盐的线粒体和细胞核效应可被抗凋亡原癌基因产物Bcl-2的过表达所抑制，并被2-溴棕榈酸盐以及肉碱所加剧。Bcl-2的细胞保护作用分别不受肉碱棕榈酰转移酶1（CPT1）抑制剂依托莫昔的拮抗，这表明最近描述的CPT1与Bcl-2之间的物理相互作用与Bcl-2介导的对棕榈酸盐诱导凋亡的抑制无关。当添加到纯化的线粒体中时，棕榈酸盐会导致可溶性因子的释放，这些因子能够在无细胞系统中刺激分离细胞核的凋亡。从过表达Bcl-2的细胞中纯化的线粒体可免受棕榈酸盐刺激的此类因子释放的影响。这些数据表明，棕榈酸盐通过对线粒体的直接作用导致细胞凋亡。
