Regulation of the human atrial myosin light chain 1 promoter by Ca2+-calmodulin-dependent signaling pathways

Item Type:	Article
Title:	Regulation of the human atrial myosin light chain 1 promoter by Ca2+-calmodulin-dependent signaling pathways
Creators Name:	Woischwill, C. and Karczewski, P. and Bartsch, H. and Luther, H.P. and Kott, M. and Haase, H. and Morano, I.
Abstract:	We investigated expression regulation of the human atrial myosin light chain 1 (hALC-1) gene using a cardiomyocyte H9c2 cell line stably transfected with a construct consisting of the human ALC-1 promoter cloned in front of the luciferase gene (H9c2T1). H9c2T1 cells were stimulated with vasopressin, which is known to induce cardiomyocyte hypertrophy and to activate a panel of signaling pathways. Those pathways involved in hALC-1 promoter activity regulation were dissected by using pharmacological inhibitor substances. Stimulation with vasopressin was associated with nuclear NFAT translocation and significantly increased human ALC-1 promoter activity. Inhibition of calcineurin by cyclosporin A blocked the effects of vasopressin on ALC-1 promoter activity to ∼50%. This suggests that the Ca2+-calmodulin-calcineurin-NFAT pathway is involved in human ALC-1 promoter activation. However, inhibition of multifunctional Ca2+-calmodulin-dependent protein kinases (CaMK) by KN-93 decreased human ALC-1 promoter activity to almost basal levels. CaMK regulation of ALC-1 promoter activity effect could well be mediated by CaMKIV, which accumulated in the nucleus upon vasopressin stimulation. Inhibition of protein kinase C (PKC) isoforms by bisindolylmaleimide had no significant influence on human ALC-1 promoter activity. Thus, our results demonstrate a dominant role of Ca2+-calmodulin-dependent signaling pathways in the regulation of human ALC-1 expression.
Keywords:	Atrial Myosin Light Chain, Ca2+ signaling, H9c2, Promoter Regulation, Animals, Rats
Source:	FASEB Journal
ISSN:	0892-6638
Publisher:	Federation of American Societies for Experimental Biology
Volume:	19
Number:	6
Page Range:	503-511
Date:	1 January 2005
Official Publication:	https://doi.org/10.1096/fj.04-2201com
PubMed:	View item in PubMed

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