RRC ID 38281
Author Shibuya K, Fukuoka J, Fujii T, Shimoda E, Shimizu T, Sakai H, Tsukada K.
Title Increase in ouabain-sensitive K+-ATPase activity in hepatocellular carcinoma by overexpression of Na+, K+-ATPase alpha 3-isoform.
Journal Eur. J. Pharmacol.
Abstract Na(+),K(+)-ATPase is a housekeeping pump in virtually all animal cells. Recently, cardiac glycosides that inhibit Na(+),K(+)-ATPase have been reported to be candidate for novel anticancer drug. Here, we investigated clinical significance of Na(+),K(+)-ATPase alpha1-isoform (alpha 1NaK), alpha2-isoform (alpha 2NaK) and alpha 3-isoform (alpha 3NaK) in hepatocellular carcinoma (HCC). Interestingly, the expression levels of alpha 3NaK protein in HCC tissues were significantly higher than those in the accompanying non-tumor tissues, whereas no significant increases in expression of alpha 1NaK and alpha 2NaK proteins were observed in HCC compared to non-tumor tissues. The ouabain (10 microM)-sensitive K(+)-ATPase activities (Na(+),K(+)-ATPase activities) in the membrane fraction from HCC tissue were significantly higher than those from non-tumor tissues. The Na(+),K(+)-ATPase activity was positively and significantly correlated with the expression level of alpha 3NaK. Apparent affinity for Na(+) in the Na(+),K(+)-ATPase activity in HCC tissues was significantly lower than that in non-tumor tissues, consistent with an elevated expression of alpha 3NaK relative to alpha 1NaK. Our results suggest that overexpression of alpha 3NaK increases the Na(+),K(+)-ATPase activity of HCC cells.
Volume 638(1-3)
Pages 42-6
Published 2010-7-25
DOI 10.1016/j.ejphar.2010.04.029
PII S0014-2999(10)00360-2
PMID 20447393
MeSH Aged Carcinoma, Hepatocellular / metabolism* Female Hep G2 Cells Humans Isoenzymes / biosynthesis Liver / metabolism* Liver Neoplasms / metabolism* Male Ouabain / pharmacology* Sodium / pharmacology Sodium-Potassium-Exchanging ATPase / metabolism* Up-Regulation*
IF 3.17
Times Cited 10
Human and Animal Cells