CA-2+-CHANNEL BLOCKERS MODULATE EXPRESSION OF 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE AND LOW-DENSITY-LIPOPROTEIN RECEPTOR GENES STIMULATED BY PLATELET-DERIVED GROWTH-FACTOR

被引：42

作者：

BLOCK, LH ^{[1
]}

MATTHYS, H ^{[1
]}

EMMONS, LR ^{[1
]}

PERRUCHOUD, A ^{[1
]}

ERNE, P ^{[1
]}

ROTH, M ^{[1
]}

机构：

[1] UNIV BASEL,KANTONSSPITAL,DEPT RES,CH-4031 BASEL,SWITZERLAND

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1991年 / 88卷 / 20期

关键词：

GENE ACTIVATION; ATHEROSCLEROSIS;

D O I：

10.1073/pnas.88.20.9041

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The effects of Ca2+-channel blockers (amlodipine, nifedipine, nitrendipine, and verapamil) on expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.88) and low density lipoprotein receptor (LDL-R) genes stimulated by recombinant platelet-derived growth factor BB isomer (PDGF-BB) were evaluated in human skin fibroblasts. The drugs enhanced expression of the LDL-R protein on the plasma membrane of the cells; in contrast, they inhibited expression of the HMG-CoA reductase gene. In addition, PDGF-BB-dependent stimulation of transcription of c-fos mRNA was inhibited also by the Ca2+-channel blockers. We conclude that PDGF-BB-dependent activation of the two genes is inhibited effectively by the Ca2+-channel blockers, at therapeutic concentrations, although they are unable to lower systemic cholesterol levels at these concentrations; however, they do modify responses of the two genes that are involved crucially in regulation of cellular cholesterol homeostasis.

引用

页码：9041 / 9045

页数：5

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