In vivo regulation of the β-myosin heavy chain gene in hypertensive rodent heart

被引:19
作者
Wright, CE [1 ]
Bodell, PW [1 ]
Haddad, F [1 ]
Qin, AX [1 ]
Baldwin, KM [1 ]
机构
[1] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2001年 / 280卷 / 05期
关键词
hypertension; transcription; dual luciferase; in vivo gene transfer;
D O I
10.1152/ajpcell.2001.280.5.C1262
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The main goal of this study was to examine the transcriptional activity of different-length beta -myosin heavy chain (beta -MHC) promoters in the hypertensive rodent heart using the direct gene transfer approach. A hypertensive state was induced by abdominal aortic constriction (AbCon) sufficient to elevate mean arterial pressure by similar to 45% relative to control. Results show that beta -MHC promoter activity of all tested wild-type constructs, i.e., -3500, -408, -299, -215, -171, and -71 bp, was significantly increased in AbCon hearts. In the normal control hearts, expression of the -71-bp construct was comparable to that of the promoterless vector, but its induction by AbCon was comparable to that of the other constructs. Additional results, based on mutation analysis and DNA gel mobility shift assays targeting beta e1, beta e2, GATA, and beta e3 elements, show that these previously defined cis-elements in the proximal promoter are indeed involved in maintaining basal promoter activity; however, none of these elements, either individually or collectively, appear to be major players in mediating the hypertension response of the beta -MHC gene. Collectively, these results indicate that three separate regions on the beta -MHC promoter are involved in the induction of the gene in response to hypertension: 1) a distal region between -408 and -3500 bp, 2) a proximal region between -299 and -215 bp, and 3) a basal region within 271 bp of the transcription start site. Future research needs to further characterize these responsive regions to more fully delineate beta -MHC transcriptional regulation in response to pressure overload.
引用
收藏
页码:C1262 / C1276
页数:15
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