Acute hypoxia increases intracellular L-arginine content in cultured porcine pulmonary artery endothelial cells
✍ Scribed by Yunchao Su; Edward R. Block
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 566 KB
- Volume
- 167
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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.