Iron-induced inhibition of Na+, K(+)-ATPase and Na+/Ca2+ exchanger in synaptosomes: protection by the pyridoindole stobadine.
The effect of oxidative stress, induced by Fe(2+)-EDTA system, on Na+,K(+)-ATPase, Na+/CA2+ exchanger and membrane fluidity of synaptosomes was investigated. Synaptosomes isolated from gerbil whole forebrain were incubated in the presence of 200 microM FeSO4-EDTA per mg of protein at 37 degrees C for 30 min. The oxidative insult reduced Na+,K(+)-ATPase activity by 50.7 +/- 5.0% and Na+/Ca2+ exchanger activity measured in potassium and choline media by 47.1 +/- 7.2% and 46.7 +/- 8.6%, respectively. Membrane fluidity was also significantly reduced as observed with the 1,6-diphenyl-1,3,5-hexatriene probe. Stobadine, a pyridoindole derivative, prevented the decrease in membrane fluidity and in Na+/Ca2+ exchanger activity. The Na+,K(+)-ATPase activity was only partially protected by this lipid antioxidant, indicating a more complex mechanism of inhibition of this protein. The results of the present study suggest that the Na+/Ca2+ exchanger and the Na+,K(+)-ATPase are involved in oxidation stress-mediated disturbances of intracellular ion homeostasis and may contribute to cell injury.
Kaplán
P
P
Department of Biochemistry, Jessenius Medical Faculty, Comenius University, Martin, Slovak Republic. kaplan@jfmed.uniba.sk
Matejovicová
M
M
Mézesová
V
V
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002243:Carbolines / Q000494:pharmacology*; D005849:Gerbillinae; D007501:Iron / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism
D002243:Carbolines; D019831:Sodium-Calcium Exchanger; D007501:Iron; D000254:Sodium-Potassium-Exchanging ATPase; C100106:dicarbine