Su Y, Block E R
Department of Medicine, University of Florida College of Medicine, Gainesville 32608, USA.
J Cell Physiol. 1996 May;167(2):349-53. doi: 10.1002/(SICI)1097-4652(199605)167:2<349::AID-JCP20>3.0.CO;2-1.
Exposure to hypoxia (0% O2) for 4-24 h resulted in increased intracellular L-arginine content and increased activity of calpain, a calcium-dependent neutral cysteine protease, in pulmonary artery endothelial cells. Calpain-inhibitor I abolished the increased L-arginine content in hypoxic cells. When endothelial cell proteins were labeled with [3H]-L-arginine and the cells exposed to hypoxia, we observed an increase in free [3H]-L-arginine and a decrease in [3H]-L-arginine-labeled proteins. Once again, calpain-inhibitor I prevented the increases in free [3H]-L-arginine and the decreases in [3H]-L-arginine-labeled proteins in hypoxic cells. Hypoxia also inhibited the synthesis of L-arginine-containing proteins. Thus, the increase in intracellular L-arginine content in hypoxic pulmonary artery endothelial cells is caused by an increase in proteolysis secondary to calpain and a decrease in protein synthesis. These results indicate that hypoxia can modulate the availability of free intracellular L-arginine, the exclusive precursor of nitric oxide (NO) and the primary substrate of NO synthase, by affecting the synthesis and degradation of cellular proteins.
将肺动脉内皮细胞暴露于低氧环境（0%氧气）4 - 24小时，会导致细胞内L - 精氨酸含量增加，同时钙蛋白酶（一种钙依赖性中性半胱氨酸蛋白酶）的活性增强。钙蛋白酶抑制剂I消除了低氧细胞中L - 精氨酸含量的增加。当用[3H] - L - 精氨酸标记内皮细胞蛋白并将细胞暴露于低氧环境时，我们观察到游离[3H] - L - 精氨酸增加，而[3H] - L - 精氨酸标记的蛋白减少。同样，钙蛋白酶抑制剂I可防止低氧细胞中游离[3H] - L - 精氨酸的增加以及[3H] - L - 精氨酸标记蛋白的减少。低氧还抑制含L - 精氨酸蛋白的合成。因此，低氧肺动脉内皮细胞内L - 精氨酸含量的增加是由钙蛋白酶介导的蛋白水解增加以及蛋白合成减少所致。这些结果表明，低氧可通过影响细胞蛋白的合成和降解来调节细胞内游离L - 精氨酸（一氧化氮（NO）的唯一前体和NO合酶的主要底物）的可用性。
