Regulation of ornithine decarboxylase and polyamine import by hypoxia in pulmonary artery endothelial cells.
In rat lung and cultured lung vascular cells, hypoxia decreases ornithine decarboxylase (ODC) activity and increases polyamine import. In this study, we used rat cultured pulmonary artery endothelial cells to explore the mechanism of hypoxia-induced reduction in ODC activity and determined whether this event was functionally related to the increase in polyamine import. Two strategies known to suppress proteasome-mediated ODC degradation, lactacystin treatment and use of cells expressing a truncated ODC incapable of interacting with the proteasome, prevented the hypoxia-induced decrease in ODC activity. Interestingly, though, cellular abundance of the 24-kDa antizyme, a known physiological accelerator of ODC degradation, was not increased by hypoxia. These observations suggest that an antizyme-independent ODC degradation pathway contributes to hypoxia-induced reductions of ODC activity. When reductions in ODC activity in hypoxia were prevented by the proteasome inhibitor strategies, hypoxia failed to increase polyamine transport. The induction of polyamine transport in hypoxic pulmonary artery endothelial cells thus seems to require decreased ODC activity as an initiating event.
Babal
Pavel
P
Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.
Ruchko
Mykhaylo
M
Ault-Ziel
Kathryn
K
Cronenberg
Lauren
L
Olson
Jack W
JW
Gillespie
Mark N
MN
D000818:Animals; D015153:Blotting, Western; D002250:Carbon Radioisotopes; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006976:Hypertension, Pulmonary / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D011073:Polyamines / Q000493:pharmacokinetics*; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000201:enzymology*; D011700:Putrescine / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013095:Spermidine / Q000493:pharmacokinetics; D013096:Spermine / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D011073:Polyamines; D011506:Proteins; D012333:RNA, Messenger; C031017:ornithine decarboxylase antizyme; D013096:Spermine; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine