Kk. Graven et al., HYPOXIC REGULATION OF ENDOTHELIAL GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE, American journal of physiology. Cell physiology, 43(2), 1998, pp. 347-355
The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
is induced by hypoxia in endothelial cells (EC). To define the mechan
isms by which GAPDH is regulated by hypoxia, EC were exposed to cobalt
, other transition metals, carbon monoxide (CO), deferoxamine, or cycl
oheximide in the presence or absence of hypoxia for 24 h, and GAPDH pr
otein 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. GAPD
H 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 prote
in phosphorylation, a calcium channel blocker, a calcium ionophore, or
alterations in redox state. GAPDH induction by hypoxia or transitiona
l metals was partially blocked by sodium nitroprusside but was not alt
ered by the inhibitor of nitric oxide synthase N-omega-nitro-L-arginin
e. These findings suggest that GAPDH induction by hypoxia in EC occurs
via mechanisms other than those involved in other hypoxia-responsive
systems.