Hypoxic regulation of endothelial glyceraldehyde-3-phosphate dehydrogenase.
The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is induced by hypoxia in endothelial cells (EC). To define the mechanisms by which GAPDH is regulated by hypoxia, EC were exposed to cobalt, other transition metals, carbon monoxide (CO), deferoxamine, or cycloheximide in the presence or absence of hypoxia for 24 h, and GAPDH protein and mRNA levels were measured. GAPDH was induced in cells by the transition metals cobalt, nickel, and manganese and by deferoxamine, and GAPDH mRNA induction by hypoxia was blocked by cycloheximide. GAPDH induction by hypoxia, unlike that of other hypoxia-regulated genes, was not inhibited by CO or by 4,6-dioxoheptanoic acid, an inhibitor of heme synthesis. GAPDH induction was not altered by mediators of protein phosphorylation, a calcium channel blocker, a calcium ionophore, or alterations in redox state. GAPDH induction by hypoxia or transitional metals was partially blocked by sodium nitroprusside but was not altered by the inhibitor of nitric oxide synthase N omega-nitro-L-arginine. These findings suggest that GAPDH induction by hypoxia in EC occurs via mechanisms other than those involved in other hypoxia-responsive systems.
Graven
K K
KK
Pulmonary Center, Boston University School of Medicine, Massachusetts 02118, USA.
McDonald
R J
RJ
Farber
H W
HW
D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis* / Q000235:genetics; D006537:Heptanoates / Q000494:pharmacology; D017895:Manganese Compounds / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D019335:Nitroarginine / Q000031:analogs & derivatives / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D017967:Zinc Compounds / Q000494:pharmacology
D000931:Antidotes; D002712:Chlorides; D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D006537:Heptanoates; D017895:Manganese Compounds; D012333:RNA, Messenger; D017967:Zinc Compounds; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D003035:Cobalt; C020804:succinylacetone; C022838:nickel chloride; D009532:Nickel; C016837:zinc chloride; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; C018021:cobaltous chloride; D003676:Deferoxamine; C025340:manganese chloride; C029451:ferrous chloride; D002118:Calcium