Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 638, Issue 1-3, Pages 42-46Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2010.04.029
Keywords
Liver; Cancer; Na+,K+-ATPase; Overexpression; Ouabain
Categories
Funding
- Japan Society for the Promotion of Science [18390064, 20010617]
- Ministry of Education, Culture, Sports, Science and Technology of Japan [18059012, 20056010]
- Grants-in-Aid for Scientific Research [18059012, 18390064, 22590201, 20056010] Funding Source: KAKEN
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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 alpha 1-isoform (alpha 1NaK), alpha 2-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 mu M)-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. (C) 2010 Elsevier B.V. All rights reserved.
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