TY - JOUR
T1 - Acute hypoxia increases intracellular L-arginine content in cultured porcine pulmonary artery enclothelial cells
AU - Su, Yunchao
AU - Block, Edward R.
PY - 1996/5
Y1 - 1996/5
N2 - 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.
AB - 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.
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U2 - 10.1002/(SICI)1097-4652(199605)167:2<349::AID-JCP20>3.0.CO;2-1
DO - 10.1002/(SICI)1097-4652(199605)167:2<349::AID-JCP20>3.0.CO;2-1
M3 - Article
C2 - 8613477
AN - SCOPUS:0029912342
SN - 0021-9541
VL - 167
SP - 349
EP - 353
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 2
ER -