HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/2/C319    most recent 00536.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Zhou, X. Articles by Fan, X. Search for Related Content PubMed PubMed Citation Articles by Zhou, X. Articles by Fan, X.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Stimulation of Na,K-ATPase by low potassium requires reactive oxygen species

¹Department of Medicine, Uniformed Services University, Bethesda 20814; ²Department of Medicine, University of Maryland, Baltimore, Maryland 21201; and ³Department of Natural Environment Sciences, Kyoto University, Kyoto 606-01, Japan

Submitted 19 November 2002 ; accepted in final form 2 April 2003

The signaling pathway that transduces the stimulatory effect of low K⁺ on the biosynthesis of Na,K-ATPase remains largely unknown. The present study was undertaken to examine whether reactive oxygen species (ROS) mediated the effect of low K⁺ in Madin-Darby canine kidney (MDCK) cells. Low K⁺ increased ROS activity in a time- and dose-dependent manner, and this effect was abrogated by catalase and N-acetylcysteine (NAC). To determine the role of ROS in low-K⁺-induced gene expression, the cells were first stably transfected with expression constructs in which the reporter gene chloramphenicol acetyl transferase (CAT) was under the control of the avian Na,K-ATPase -subunit 1.9 kb and 900-bp 5'-flanking regions that have a negative regulatory element. Low K⁺ increased the CAT expression in both constructs. Catalase or NAC inhibited the effect of low K⁺. To determine whether the increased CAT activity was mediated through releasing the repressive effect or a direct stimulation of the promoter, the cells were transfected with a CAT expression construct directed by a 96-bp promoter fragment that has no negative regulatory element. Low K⁺ also augmented the CAT activity expressed by this construct. More importantly, both catalase and NAC abolished the effect of low K⁺. Moreover, catalase and NAC also inhibited low-K⁺-induced increases in the Na,K-ATPase ₁- and ₁-subunit protein abundance and ouabain binding sites. The antioxidants had no significant effect on the basal levels of CAT activity, protein abundance, or ouabain binding sites. In conclusion, low K⁺ enhances the Na,K-ATPase gene expression by a direct stimulation of the promoter activity, and ROS mediate this stimulation and also low-K⁺-induced increases in the Na,K-ATPase protein contents and cell surface molecules.

Madin-Darby canine kidney cells; N-acetylcysteine; catalase

This article has been cited by other articles:

				T. Mijatovic, N. De Neve, P. Gailly, V. Mathieu, B. Haibe-Kains, G. Bontempi, J. Lapeira, C. Decaestecker, V. Facchini, and R. Kiss Nucleolus and c-Myc: potential targets of cardenolide-mediated antitumor activity Mol. Cancer Ther., May 1, 2008; 7(5): 1285 - 1296. [Abstract] [Full Text] [PDF]

				S. Vylkova, W. S. Jang, W. Li, N. Nayyar, and M. Edgerton Histatin 5 Initiates Osmotic Stress Response in Candida albicans via Activation of the Hog1 Mitogen-Activated Protein Kinase Pathway Eukaryot. Cell, October 1, 2007; 6(10): 1876 - 1888. [Abstract] [Full Text] [PDF]

				D. Wunder, J. Dong, D. Baev, and M. Edgerton Human Salivary Histatin 5 Fungicidal Action Does Not Induce Programmed Cell Death Pathways in Candida albicans Antimicrob. Agents Chemother., January 1, 2004; 48(1): 110 - 115. [Abstract] [Full Text] [PDF]