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In vascular smooth muscle cells and several other cell types, inhibition of Na + ⁄K + -ATPase leads to the expression of early response genes, including c-Fos. We designed this study to examine whether or not a putative Na + i ⁄K + i-sensitive element is located within the c-Fos5¢-UTR from )650 to +103 containing all known response elements activated by ‘classic’ stimuli, such as growth factors and Ca 2+ i-raising compounds. | ỊFEBS Journal Na i-induced c-Fos expression is not mediated by activation of the 5 -promoter containing known transcriptional elements Mounsif Halou Sebastien Taurin1 2 z Olga A. Akimova1 Deng-Fu Guo1 Johanne Tremblay1 Nickolai O. Dulin2 Pavel Hamet1 and Sergei N. Orlov1 1 Centre de recherche Centre hospitalier de l Universite de Montreal CHUM - Technopole ANGUS Montreal PQ Canada 2 Department of Medicine University of Chicago Chicago IL USA Keywords c-Fos expression intracellular Na ouabain 5 -UTR Correspondence S. N. Orlov Centre de recherche CHUM - Technopole ANGUS 2901 Rachel est Montreal Quebec H1W 4A4 Canada Fax 1 514 412 7638 Tel 1 514 890 8000 E-mail sergei.n.orlov@umontreal.ca These authors contributed equally to this work Received 4 January 2007 revised 25 April 2007 accepted 16 May 2007 doi 10.1111 j.1742-4658.2007.05885.x In vascular smooth muscle cells and several other cell types inhibition of Na K -ATPase leads to the expression of early response genes including c-Fos. We designed this study to examine whether or not a putative Na i K i-sensitive element is located within the c-Fos 5 -UTR from - 650 to 103 containing all known response elements activated by classic stimuli such as growth factors and Ca2 i-raising compounds. In HeLa cells the highest increment of c-Fos mRNA content was noted after 6 h of Na K -ATPase inhibition with ouabain that was abolished by actinomycin D an inhibitor of RNA synthesis. c-Fos protein accumulation in ouabain-treated cells correlated with a gain of Na i and loss of K i. Augmented c-Fos expression was also observed under inhibition of Na K -ATPase in K -free medium and in the presence of the Na ionophore monensin. The effect of ouabain on c-Fos expression was sharply attenuated under dissipation of the transmembrane Na gradient but was preserved in the presence of Ca2 chelators and the extracellular regulated kinase inhibitor PD98059 thus indicating an Na i-mediated Ca2 i- and extracellular regulated .
