Control of Sodium/Proton Exchange by Plasma Membrane Electron Transport
External electron acceptors activate proton release from many animal cell types. Ferricyanide induced proton release has been described 1, 2, 3. Ferric ions loosly associated with diferric transferrin are even more efficient in stimulation of proton release than is ferricyanide, in that they give a higher ratio of protons released to electrons transferred4. Release of up to 100 protons per electron transferred has been observed. Inhibitors of plasma membrane electron transport such as adriamycin or bleomycin inhibit proton release5, 6. Since the ratio of protons released to ferric transferrin reduced greatly exceeds 1 or 2, which would be expected of a redox coupled proton pump, proton transfer through a redox activated channel is most likely. Following studies by R. Garcia-Caöero, J. Diaz-Gil and M. Guerra which presented evidence that the oxidant induced proton release is dependent on the Na+/H+ exchange system, we find that ferric ion induced proton release with pineal or HeLa cells is dependent on external Na+ ions and is inhibited by amiloride and amiloride analogs. Apotransferrin does not induce proton release. Inhibition of ferric ion reduction by apotransferrin or monoclonal antibodies to the transferrin receptor (B3/25, GB16) prevents induction of proton release, which indicates that the transferrin receptor is involved in the maximum redox activation of the Na+/H+ exchange. Ferricyanide reduction is less dependent on the transferrin receptor and is less efficient in induction of proton release. We propose that oxidant of cytosolic NADH by the transmembrane dehydrogenase can provide a proton for activation of the Na+/H+ antiport7 and that localized proton movement may be favored by the presence of the transferrin receptor. Activation of proton release by impermeable oxidant has been observed with 3T3, SV40 transformed 3T3, rat liver, BK, HL60 and human erythroleukemia cells in addition to HeLa and rat pineal cells.
KeywordsProton Transfer Transferrin Receptor Proton Release Redox Activation Endocrinology Department
- 5.I.L. Sun and F.L. Crane. Proc. Indiana Acad. Sci. 93, 267 (1984)Google Scholar