Increase in ouabain-sensitive K+-ATPase activity in hepatocellular carcinoma by overexpression of Na+, K+-ATPase alpha 3-isoform.
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| 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.
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| Authors | Kazuto Shibuya, Junya Fukuoka, Takuto Fujii, Eri Shimoda, Takahiro Shimizu, Hideki Sakai, Kazuhiro Tsukada |
| Journal | European journal of pharmacology (Eur J Pharmacol) Vol. 638 Issue 1-3 Pg. 42-6 (Jul 25 2010) ISSN: 1879-0712 [Electronic] Netherlands |
| PMID | 20447393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | (c) 2010 Elsevier B.V. All rights reserved. |
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