Characterization of Ca(2+) flows essential in ornithine decarboxylase induction by L-asparagine in rat hepatoma cells using Ca(2+) flow inhibitors.
L-Asparagine stimulates bi-directional Ca(2+) flows and induces ornithine decarboxylase in Reuber H-35 hepatoma cells. Previously it has been shown that these effects are completely, but reversibly inhibited by lanthanum chloride. In this study we examined the role(s) of Ca(2+) flows using more specific Ca(2+) flow inhibitors. It was shown that ornithine decarboxylase induction was inhibited by CdCl(2) and verapamil at concentrations above 1 mu M and 100 mu M respectively, but was unaffected by as much as 300 mu M NiCl(2), 1 mM nifedipine, or 10 mu M omega-conotoxin. Enzyme induction was blocked by the Ca(2+)-ATPase pump antagonists vanadate and Compound 48/80 in a dose-dependent manner. These results, taken together with the observations that extracellular Ca(2+) is essential for enzyme induction but a substantial elevation of cytoplasmic [Ca(2+)] is not, suggest that Ca(2+) inflow independent of the receptor-activated Ca(2+) channels, and the Ca(2+)-ATPase mediated Ca(2+) out-flow, are both important factors in the action of L-asparagine.
Wong
P C
PC
Department of Biochemistry, The University of Hong Kong, Hong Kong.
Hau
K P
KP
Pong
H H
HH
Kwok
P P
PP
Fong
W F
WF
D000818:Animals; D001216:Asparagine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
D001216:Asparagine; D009955:Ornithine Decarboxylase; D002118:Calcium