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Molecular Biological Study of Cardiomyopathy in animals and in human

动物和人类心肌病的分子生物学研究

基本信息

批准号：
03454255
负责人：
AZUMA Junichi
金额：
$ 3.33万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454255/
关键词：
Cardiomyopathy Myopathic hamster Oncogene Familial hypertrophic cardiomyopathy Myosin heavy chain gene Genetic disease Point mutation Myocardial hypertrophy 肥大型心筋症ミオシン重鎖点変異 DNA プレアルブミン心筋症ハムスタ-α受容体 mRNA 突然変異

项目摘要

The expression of immediate early gene (c-fos mRNA) was transiently induced after norepinephirine (NE) treatment in hamster hearts in vivo as well as in cultured neonatal rat myocytes. The expression of c-fos mRNA in the heart was more augmented in cardiomyopathic hamster(Bio 14.6) than in control hamster (RB) after 1.5 mg/kg of NE injection. Treadmill running for 1 hr after NE(0.1mg/kg) injection induced the expression of c-fos mRNA in the Bio 14.6 heart but not in RB heart. The mRNA level of alpha_1 adrenergic receptor was not increased in Bio 14.6 heart compared to that of RB heart. The present results suggest that the post-receptor enhancement of signal transduction pathway after alpha_1 adrenergic receptor in cardiomyopathic hamster heart, and the profitable management for cardiomyopathic patients with alpha_1 blocking agents.The cardiac beta-myosin heavy chain (beta-MHC) gene was analyzed in Japanese patients with familial hypertrophic cardiomyopathy(HCM). We found missence mutation (606Val -> Met) of beta-MHC, which has been reported in several Caucasian HCM families. Another kind of mutation, found in Japanese for the first time, was the deletion of three nucleotides of 10th codon in the exon 3, which results in the delection of an amino acid, glycine. Although the analysis of beta-MHC gene could lead to the predicition of prognosis of the patients with HCM, we don't have effective therapy regimen yet, which is eagerly hunting for.

去甲肾上腺素（NE）瞬时诱导仓鼠心脏和培养的新生大鼠心肌细胞中立即早期基因（c-fos mRNA）的表达。注射1.5 mg/kg NE后，心肌病仓鼠（Bio 14.6）心脏中c-fos mRNA的表达比对照仓鼠（RB）增强。注射NE（0.1mg/kg）后，在跑步机上运动1小时可诱导Bio 14.6心脏c-fos mRNA的表达，而在RB心脏中无表达。与RB心脏相比，Bio 14.6心脏α _1肾上腺素能受体mRNA水平没有升高。本研究结果提示心肌病仓鼠心脏α _1肾上腺素能受体后信号转导通路的受体后增强，以及α _1阻滞剂对心肌病患者的有益管理。分析了日本家族性肥厚性心肌病（HCM）患者的心肌β -肌球蛋白重链（β - mhc）基因。我们发现了在几个高加索HCM家族中报道的β - mhc缺失突变（606Val -> Met）。在日本首次发现的另一种突变是，在第3外显子的第10个密码子的三个核苷酸缺失，导致氨基酸甘氨酸的缺失。虽然通过对β - mhc基因的分析可以预测HCM患者的预后，但我们目前还没有有效的治疗方案，这是迫切需要的。