Morales M P, Gálvez A, Eltit J M, Ocaranza P, Díaz-Araya G, Lavandero S
Department of Biochemistry and Molecular Biology, University of Chile, Santiago, 6640750, Chile.
Biochem Biophys Res Commun. 2000 Apr 21;270(3):1029-35. doi: 10.1006/bbrc.2000.2550.
Insulin-like growth factor-1 (IGF-1) is a natural protectant of cardiac myocytes that has been shown to improve cardiac function. The role of IGF-1 in attenuating apoptosis induced by osmotic stress (sorbitol, SOR) or by other known apoptotic stimuli (doxorubicin, angiotensin II, and serum withdrawal) was determined in cultured cardiac myocytes. After 6 h of exposure to SOR, apoptosis was initiated, concomitant with a decrease in cell survival and increases in poly-[ADP-ribose] polymerase (PARP) degradation and DNA fragmentation. These effects were maximal after 24 h. IGF-1 partially attenuated apoptosis induced by sorbitol but not that induced by angiotensin II, doxorubicin, or serum withdrawal. In cells preincubated with IGF-1 before the addition of SOR, we detected an increase in the number of viable cells, a decrease in the generation of DNA fragments on agarose gel electrophoresis and in the percentage of positive TUNEL cells, and a reduction on PARP levels. These results suggest that IGF-1 prevents apoptosis induced by osmotic stress in cardiac myocytes but not apoptosis induced by doxorubicin and angiotensin II.
胰岛素样生长因子-1（IGF-1）是心肌细胞的一种天然保护剂，已被证明可改善心脏功能。在培养的心肌细胞中确定了IGF-1在减轻由渗透压应激（山梨醇，SOR）或其他已知凋亡刺激（阿霉素、血管紧张素II和血清去除）诱导的凋亡中的作用。暴露于SOR 6小时后，凋亡开始，同时细胞存活率降低，聚[ADP-核糖]聚合酶（PARP）降解和DNA片段化增加。这些效应在24小时后达到最大。IGF-1部分减轻了山梨醇诱导的凋亡，但未减轻阿霉素、血管紧张素II或血清去除诱导的凋亡。在添加SOR之前用IGF-1预孵育的细胞中，我们检测到存活细胞数量增加，琼脂糖凝胶电泳上DNA片段的产生减少以及TUNEL阳性细胞的百分比降低，并且PARP水平降低。这些结果表明，IGF-1可预防心肌细胞中由渗透压应激诱导的凋亡，但不能预防阿霉素和血管紧张素II诱导的凋亡。
