Possible Role of Transplasma Membrane Ferricyanide Reductase in Mitogenic Activation of Rat Liver Cells
Transplasma ferricyanide reductase of hepatocytes is activated by the specific mitogen, r-LGF, immediately upon addition, in a sodium-dependent, amiloride-sensitive way. The above phenomenon seems to be transient, and is abolished when the sodium gradient is reversed. Ferricyanide activates H+ efflux and 22Na uptake in parallel fashion. Ferricyanide by itself increases 22Na uptake and H+ efflux, and the natural substrate for the redox enzyme, diferric transferrin, increases DNA synthesis when added, together with submaximal doses of r-LGF, to cultured hepatocytes.
Phorbol esters such as TPA fail to activate ferricyanide reductase, and r-LGF is able to further activate 22Na uptake in hepatocytes previously treated with TPA for 24 hours. Neither r-LGF nor ferricyanide promotes any change in the levels of soluble protein kinase C, nor do trifluoperazine, isobutylmethylxantine, A23187 or H-7 decrease significantly the basal redox activity.
The above data point out substantial differences between the natural mitogen, r-LGF, and that hypothesized for phorbol esters via protein kinase C with regard to the early activation of Na uptake in hepatocytes.
KeywordsReductase Activity Phorbol Ester Inositol Trisphosphate Submaximal Dose Diferric Transferrin
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