c-Fos expression in ouabain-treated vascular smooth muscle cells from rat aorta: Evidence for an intracellular-sodium-mediated, calcium-independent mechanism

Taurin, Sebastien, Dulin, Nickolai O., Pchejetski, Dmitry, Grygorczyk, Ryszard, Tremblay, Johanne, Hamet, Pavel and Orlov, Sergei N. (2002) c-Fos expression in ouabain-treated vascular smooth muscle cells from rat aorta: Evidence for an intracellular-sodium-mediated, calcium-independent mechanism. The Journal of Physiology, 543 (3). pp. 835-47. ISSN 0022-3751

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Abstract

In this study, we examined the effect of Na(+)-K(+) pump inhibition on the expression of early response genes in vascular smooth muscle cells (VSMC) as possible intermediates of the massive RNA synthesis and protection against apoptosis seen in ouabain-treated VSMC in our previous experiments. Incubation of VSMC with ouabain resulted in rapid induction of c-Fos protein expression with an approximately sixfold elevation after 2 h of incubation. c-Jun expression was increased by approximately fourfold after 12 h, whereas expression of activating transcription factor 2, cAMP/Ca(2+) response element binding protein (CREB)-1 and c-Myc was not altered. Markedly augmented c-Fos expression was also observed under Na(+)-K(+) pump inhibition in potassium-depleted medium. Na(+)-K(+) pump inhibition triggered c-Fos expression via elevation of the [Na(+)](i)/[K(+)](i) ratio. This conclusion follows from experiments showing the lack of effect of ouabain on c-Fos expression in high-potassium-low-sodium medium and from the comparison of dose responses of Na(+)-K(+) pump activity, [Na(+)](i) and [K(+)](i) content and c-Fos expression to ouabain. A fourfold increment of c-Fos mRNA was revealed 30 min following addition of ouabain to the incubation medium. At this time point, treatment with ouabain resulted in an approximately fourfold elevation of [Na(+)](i) but did not affect [K(+)](i). Augmented c-Fos expression was also observed under VSMC depolarization in high-potassium medium. Increments in both c-Fos expression and (45)Ca uptake in depolarized VSMC were abolished under inhibition of L-type Ca(2+) channels with 0.1 microM nicardipine. Ouabain did not affect the free [Ca(2+)](i) or the content of exchangeable [Ca(2+)](i). Ouabain-induced c-Fos expression was also insensitive to the presence of nicardipine and [Ca(2+)](o), as well as chelators of [Ca(2+)](o) (EGTA) and [Ca(2+)](i) (BAPTA). The effect of ouabain and serum on c-Fos expression was additive. In contrast to serum, however, ouabain failed to activate the Elk-1, serum response factor, CREB and activator protein-1 transcription factors identified within the c-Fos promoter. These results suggest that Na(+)-K(+) pump inhibition triggers c-Fos expression via [Na(+)](i)-sensitive [Ca(2+)](i)-independent transcription factor(s) distinct from factors interacting with known response elements of this gene promoter.

Item Type:	Article
Uncontrolled Keywords:	animals,aorta,blood proteins,calcium,cells, cultured,enzyme inhibitors,gene expression,hydrogen-ion concentration,muscle, smooth, vascular,ouabain,potassium,proto-oncogene proteins c-fos,rats,rats, inbred bn,response elements,sodium,sodium-potassium-exchanging atpase,transcription factors
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Pure Connector
Date Deposited:	16 Dec 2014 10:12
Last Modified:	08 Sep 2023 13:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/51548
DOI:	10.1113/jphysiol.2002.023259

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