Calmodulin effects on steroids-regulated plasma membrane calcium pump activity.
It is now generally accepted that non-genomic steroids action precedes their genomic effects by modulation of intracellular signaling pathways within seconds after application. Ca(2+) is a very potent and ubiquitous ion in all cells, and its concentration is precisely regulated. The most sensitive on Ca(2+) increase is ATP-consuming plasma membrane calcium pump (PMCA). The enzyme is coded by four genes, but isoforms diversity was detected in excitable and non-excitable cells. It is the only ion pump stimulated directly by calmodulin (CaM). We examined the role of PMCA isoforms composition and CaM effect in regulation of Ca(2+) uptake by estradiol, dehydroepiandrosterone (DHEA), pregnenolone (PREG), and their sulfates in a concentration range from 10(-9) to 10(-6) M, using the membranes from rat cortical synaptosomes, differentiated PC12 cells, and human erythrocytes. In excitable membranes with full set of PMCAs steroids apparently increased Ca(2+) uptake, although to a variable extent. In most of the cases, CaM decreased transport by 30-40% below controls. Erythrocyte PMCA was regulated by the steroids somewhat differently than excitable cells. CaM strongly increased the potency for Ca(2+) extrusion in membranes incubated with 17-beta-estradiol and PREG. Our results indicated that steroids may sufficiently control cytoplasmic calcium concentration within physiological and therapeutic range. The response depended on the cell type, PMCA isoforms expression profile, CaM presence, and the steroids structure.
Zylinska
Ludmila
L
Department of Molecular Neurochemistry, Medical University, Lodz, Poland. luska@csk.umed.lodz.pl
Kowalska
Iwona
I
Ferenc
Bozena
B
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D016716:PC12 Cells; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D013256:Steroids / Q000378:metabolism*
D002147:Calmodulin; D007527:Isoenzymes; D013256:Steroids; D053499:Plasma Membrane Calcium-Transporting ATPases; D002118:Calcium