title: Acute hypoxia increases intracellular L-arginine content in cultured porcine pulmonary artery endothelial cells.
abstract: 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.
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Gainesville 32608, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Su
authors.forename: E R
authors.initials: ER
authors.lastname: Block
mesh_terms: D000818:Animals; D001120:Arginine / Q000096:biosynthesis / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D011506:Proteins / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology; D013552:Swine
chemical_list: D011506:Proteins; D001120:Arginine; D010450:Endopeptidases; D002154:Calpain