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1,25-二羟维生素D3对HL-1心肌细胞的细胞增殖、大小、基因表达及受体定位的作用

1,25(OH)2-vitamin D3 actions on cell proliferation, size, gene expression, and receptor localization, in the HL-1 cardiac myocyte.

作者信息

Nibbelink Karl A, Tishkoff Daniel X, Hershey Stephen D, Rahman Ayesha, Simpson Robert U

机构信息

Department of Pharmacology, University of Michigan School of Medicine, 1301 MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0632, USA.

出版信息

J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):533-7. doi: 10.1016/j.jsbmb.2006.12.099. Epub 2006 Dec 23.

Abstract

The steroid hormone 1,25(OH)(2)-vitamin D(3) [1,25D] has been shown to affect the growth and proliferation of primary cultures of ventricular myocytes isolated from neonatal rat hearts. The research presented here shows that the vitamin D receptor [VDR] is present in murine cardiac myocytes (HL-1 cells), and that 1,25D affects the growth, proliferation and morphology of these cells. In addition we show that 1,25D effects expression of ANP, myotrophin, and c-myc. Furthermore, 1,25D effects expression and localization of the VDR within the cell. Murine HL-1 cardiac myocytes were grown and treated with 1,25D in culture, and growth and morphology were assessed with microscopic analysis. Cells were counted and protein levels were evaluated through Western blot analysis. Subcellular localization of the VDR was determined using immunofluorescence and confocal microscopy. 1,25D was found to decrease proliferation and alter cellular morphology of the HL-1 cells. Treatment with 1,25D increased expression of myotrophin while decreasing expression of atrial natriuretic peptide [ANP] and c-myc. 1,25D treatment also increased expression and nuclear localization of the VDR in these cardiac myocytes. Thus 1,25D is an important hormone involved in modulating and maintaining heart cell structure and function.

摘要

类固醇激素1,25(OH)₂-维生素D₃[1,25D]已被证明可影响从新生大鼠心脏分离的心室肌细胞原代培养物的生长和增殖。此处呈现的研究表明,维生素D受体[VDR]存在于小鼠心肌细胞(HL-1细胞)中,且1,25D会影响这些细胞的生长、增殖和形态。此外,我们还表明1,25D会影响心钠素(ANP)、肌养蛋白和c-myc的表达。再者,1,25D会影响VDR在细胞内的表达和定位。在培养中培养小鼠HL-1心肌细胞并用1,25D进行处理,通过显微镜分析评估生长和形态。对细胞进行计数,并通过蛋白质印迹分析评估蛋白质水平。使用免疫荧光和共聚焦显微镜确定VDR的亚细胞定位。发现1,25D可减少HL-1细胞的增殖并改变细胞形态。用1,25D处理可增加肌养蛋白的表达,同时降低心钠素[ANP]和c-myc的表达。1,25D处理还可增加这些心肌细胞中VDR的表达和核定位。因此,1,25D是一种参与调节和维持心脏细胞结构与功能的重要激素。

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