Moalic J M, Bourgeois F, Mansier P, Machida C A, Carré F, Chevalier B, Pitarque P, Swynghedauw B
Unité 127 INSERM, Hôpital Lariboisière, Paris, France.
Cardiovasc Res. 1993 Feb;27(2):231-7. doi: 10.1093/cvr/27.2.231.
The aim of this study was to determine the expression of genes coding for the beta 1 adrenergic receptor and the alpha subunit of Gs in the adult rat normal and hypertrophied left ventricle, and in the left ventricle of the hypophysectomised rat after T4 intoxication.
Total RNA was extracted from normal, control, or hypertrophied left ventricles 5 weeks after aortic stenosis, and from left ventricles of control or T4 injected hypophysectomised animals. The expression of beta 1 adrenergic receptor and G alpha s mRNAs was quantitated by northern blot analysis and hybridisation with specific 32P-dCTP labelled DNA probes.
beta 1 Adrenergic receptor mRNA was decreased (by 33%) in compensated left ventricular hypertrophy without modification of the relative level of G alpha s mRNA. The relative level of beta 1 adrenergic receptor mRNA correlated negatively with the degree of left ventricular hypertrophy, suggesting that the expression of the beta 1 adrenergic receptor gene is not activated by pressure overload. In the left ventricle of the hypophysectomised rat, a rapid increase in beta 1 adrenergic receptor mRNA (by 180% 3 h after hormone injection) was observed in response to T4, with no change in the relative content of G alpha s mRNA. These results provide evidence that beta 1 adrenergic receptor mRNA and G alpha s mRNA accumulate to different levels of abundance in the adult left ventricle, as indicated by their ratios (0.053 and 0.043 in sham operated and hypertrophied left ventricles respectively). This suggests that distinct mechanisms are involved in the control of the accumulation of these two mRNAs in cardiac tissue.
The reduction in beta 1 adrenergic receptor density in the hypertrophied rat left ventricle is associated with a parallel reduction in the level of beta 1 adrenergic receptor mRNA. The beta 1 adrenergic receptor gene may belong to a group of genes which are not activated by pressure overload, but are responsive to thyroid hormone.
本研究旨在测定编码β1肾上腺素能受体和Gsα亚基的基因在成年大鼠正常及肥厚左心室,以及甲状腺素中毒的垂体切除大鼠左心室中的表达情况。
从主动脉缩窄5周后的正常、对照或肥厚左心室,以及对照或注射甲状腺素的垂体切除动物的左心室中提取总RNA。通过Northern印迹分析及与特异性32P-dCTP标记的DNA探针杂交来定量β1肾上腺素能受体和Gαs mRNA的表达。
在代偿性左心室肥厚中,β1肾上腺素能受体mRNA减少(33%),而Gαs mRNA的相对水平未改变。β1肾上腺素能受体mRNA的相对水平与左心室肥厚程度呈负相关,提示β1肾上腺素能受体基因的表达不受压力超负荷激活。在垂体切除大鼠的左心室中,注射激素3小时后,β1肾上腺素能受体mRNA迅速增加(180%),而Gαs mRNA的相对含量无变化。这些结果表明,β1肾上腺素能受体mRNA和Gαs mRNA在成年左心室中积累到不同的丰度水平,其比例分别为假手术和肥厚左心室中的0.053和0.043。这提示在心脏组织中,这两种mRNA积累的调控涉及不同机制。
肥厚大鼠左心室中β1肾上腺素能受体密度的降低与β1肾上腺素能受体mRNA水平的平行降低相关。β1肾上腺素能受体基因可能属于一组不受压力超负荷激活,但对甲状腺激素有反应的基因。