EFFECT OF CAFFEINE ON EXPRESSION OF CARDIAC MYOSIN HEAVY-CHAIN GENE IN ADULT HYPOTHYROID AND FETAL RATS
EFFECT OF CAFFEINE ON EXPRESSION OF CARDIAC MYOSIN HEAVY-CHAIN GENE IN ADULT HYPOTHYROID AND FETAL RATS
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DOI：
10.1161/01.res.71.5.1031
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发表时间：
1992-11-01
影响因子：
20.1
通讯作者：
MATSUOKA, R
中科院分区：
文献类型：
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作者：
IMAMURA, S;KIMURA, M;MATSUOKA, R
心肌肌球蛋白重链 (MHC) 基因表达和同工酶转换的变化已被证明是由发育变化、血流动力学超负荷或各种激素的活性引起的。在这项研究中，为了检查对胎儿心血管系统有致畸作用的咖啡因是否会导致心脏 MHC 表型的分布，如果是的话，为了评估咖啡因导致心脏 MHC 表型分布的机制，我们使用以下方法在基因和蛋白质水平上检查了咖啡因、茶碱和 cAMP 对心脏 MHC 同工型转变的影响： 甲状腺功能减退的成年大鼠。此外，我们还检查了母鼠摄入咖啡因的胎儿心肌中α-和β-MHC 基因的表达。结果表明，咖啡因、茶碱和 cAMP 会导致 α-MHC mRNA 和 MHC 同工酶 V1 的积累。此外，在胎儿心脏中，人们发现咖啡因会诱导 α-MHC 基因表达的积累，这一点在母鼠中也可见到。然而，咖啡因对胎儿心脏的影响比母鼠更强。通过给予咖啡因、茶碱或cAMP，细胞内cAMP浓度增加，并且其水平与α-MHC mRNA的水平呈正相关。这些结果表明，通过施用咖啡因诱导α-MHC mRNA表达可能是通过细胞内cAMP浓度的增加来诱导的。
Changes in cardiac myosin heavy chain (MHC) gene expression and isozyme transitions have been shown to be caused by developmental changes, hemodynamic overload, or the activity of various hormones. In this study, to examine whether caffeine, which has teratogenic effects on the fetal cardiovascular system, causes the distribution of cardiac MHC phenotype and, if so, to evaluate the mechanisms of the distribution of cardiac MHC phenotype by caffeine, we examined the effects of caffeine, theophylline, and cAMP on the cardiac MHC isoform transitions at the gene and protein levels using hypothyroid adult rats. Furthermore, we examined the expression of alpha- and beta-MHC gene in cardiac muscles of fetuses whose dams had received caffeine. The results showed that caffeine, theophylline, and cAMP caused accumulations of alpha-MHC mRNA and MHC isozyme V1. Furthermore, in the fetal hearts, it was recognized that caffeine induced an accumulation of alpha-MHC gene expression, as was also seen in the dams. However, this effect of caffeine on the heart was stronger in the fetus than in the dam. Intracellular cAMP concentration was increased by the administration of caffeine, theophylline, or cAMP, and the levels showed a positive correlation with those of alpha-MHC mRNA. These results suggest that the induction of alpha-MHC mRNA expression by the administration of caffeine may be induced by an increase in intracellular cAMP concentration.