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自发性高血压大鼠中,血管特异性增加的外显子1B编码的CAV1.2通道。

Vascular-specific increase in exon 1B-encoded CAV1.2 channels in spontaneously hypertensive rats.

作者信息

Wang Wen-Ze, Saada Nehad, Dai Bosong, Pang Li, Palade Philip

机构信息

Department Neuroscience & Cell Biology, University of Texas Medical Branch, Galveston, Texas, USA.

出版信息

Am J Hypertens. 2006 Aug;19(8):823-31. doi: 10.1016/j.amjhyper.2006.01.020.

Abstract

BACKGROUND

The vasculature of the adult spontaneously hypertensive rat (SHR) is known to express more functional L-type Ca channels than the vasculature of normotensive Wistar Kyoto (WKY) rats, but it is not known which Ca(V)1.2 channel isoform is upregulated.

METHODS

Western blots and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were used to compare the expression levels of Ca(V)1.2 channel protein and message in selected tissues of adult SHR and WKY rats.

RESULTS

The results indicate overexpression in SHR vasculature specifically of the short exon 1b-encoded amino terminus Ca(V)1.2 isoform. Brain and visceral smooth muscle expressing the same isoform were not similarly affected. Differences in message levels are insufficient to account for the differences in isoform-specific protein levels.

CONCLUSIONS

We conclude that SHR vasculature must regulate the channel postranscriptionally. Further experiments will be required to determine whether this involves translation of protein from exon 1b-specific transcripts more efficiently, posttranslational chaperoning to the surface membrane more efficiently, or selective degradation of the short amino terminus form of the protein more slowly than in WKY vasculature.

摘要

背景

已知成年自发性高血压大鼠(SHR)的血管比正常血压的Wistar Kyoto(WKY)大鼠的血管表达更多功能性L型钙通道,但尚不清楚哪种Ca(V)1.2通道亚型上调。

方法

采用蛋白质免疫印迹法和实时逆转录聚合酶链反应(RT-PCR)比较成年SHR和WKY大鼠选定组织中Ca(V)1.2通道蛋白和信使核糖核酸的表达水平。

结果

结果表明,在SHR血管中,短外显子1b编码的氨基末端Ca(V)1.2亚型特异性过表达。表达相同亚型的脑和内脏平滑肌未受到类似影响。信使核糖核酸水平的差异不足以解释亚型特异性蛋白水平的差异。

结论

我们得出结论,SHR血管必须在转录后调节该通道。需要进一步实验来确定这是否涉及更有效地从外显子1b特异性转录本翻译蛋白质、更有效地将翻译后伴侣蛋白转运到表面膜,或比WKY血管更缓慢地选择性降解该蛋白的短氨基末端形式。

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