Gender-specific differences in expression of mRNAs for functional and structural proteins in rat ventricular myocardium.
Gender-specific differences in expression of mRNAs for functional and structural proteins in rat ventricular myocardium.
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大鼠心室肌功能和结构蛋白 mRNA 表达的性别特异性差异。
DOI：
10.1006/jmcc.1994.1029
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发表时间：
1994
影响因子：
5
通讯作者：
Eghbali,M
中科院分区：
文献类型：
--
作者：
Rosenkranz-Weiss,P;Tomek,RJ;Mathew,J;Eghbali,M
与性别有关的心脏病易感性的差异早已被认识到。这种差异的分子和细胞基础是未知的。在这项研究中，我们比较了基因表达的各种结构和功能蛋白质的肌肉和心肌间质室在成年和新生儿，雄性和雌性大鼠心脏。我们还比较了培养的心脏成纤维细胞从男性和女性的心脏方面的基因表达和增殖能力。结果表明，在成年大鼠心脏中，收缩蛋白α-和β-肌球蛋白重链（MHC）的mRNA丰度在雌性大鼠高于同龄雄性大鼠。而α-MHC mRNA表达水平的差异（736%，P < 0.001）明显大于β-MHC（469%，P < 0.001）。雌鼠心脏肌节肌动蛋白mRNA水平高79%（P< 0.001）。Ⅰ型胶原mRNA在雌性心脏中的表达量显著高于雄性心脏（303%，P < 0.01）。女性心脏TGF-β1、细胞骨架肌动蛋白和连接蛋白43的mRNA水平也高于男性心脏（分别为150%，P <0.01; 130%，P < 0.01和150%，P < 0.01）。新生雄性和雌性同窝仔心室组织中上述蛋白质的mRNA水平没有明显的性别相关差异。在细胞水平上，从成年和新生儿心脏中获得的心脏成纤维细胞在I型胶原、TGF-β 1或细胞骨架肌动蛋白的mRNA丰度方面具有可比性。用[3 H]胸腺嘧啶核苷掺入法测定，成年雌性大鼠心肌细胞的DNA合成量高于成年雄性大鼠心肌细胞（328%，P < 0.01）。从新生雌性大鼠心脏中获得的成纤维细胞的这种差异（933%，P < 0.001）比从新生雄性大鼠心脏中获得的细胞更明显。总之，这些发现表明，心脏组织中大多数主要蛋白质的基因表达存在性别相关差异，并且这种现象与青春期后有关。这些发现进一步表明，性别相关的差异基因表达和DNA合成的心脏细胞是由于男性和女性特异性激素的调节作用。
Sex-related differences in predisposition to heart diseases have long been recognized. The molecular and cellular bases for this differences are unknown. In this study we have compared expression of genes for various structural and functional proteins of muscle and interstitial compartments of the myocardium in the adult and neonatal, male and female rat heart. We have also compared cultured cardiac fibroblasts from male and female hearts with regards to gene expression and proliferative capacity. We showed that in the adult rats, the abundance of mRNAs for contractile proteins α- and β-myosin heavy chain (MHC) is higher in the heart of female rats than in that of age-matched male rats. However, the difference in mRNA level for α-MHC was more drastic (736%,P< 0.001) than that for β-MHC (469%P< 0.001). mRNA levels for sarcomeric actin in the female heart were greater by 79% (P< 0.001). Collagen type I had a significantly higher (303%,P< 0.01) mRNA level in the female heart compared with the male heart. mRNAs for TGF-β1, cytoskeletal actin and connexin 43 were also higher (150%,P< 0.01; 130%,P< 0.01, and 150%,P< 0.01, respectively) in the female heart compared with age-matched male heart. There were no significant sex-related differences at the mRNA levels for the above proteins in ventricular tissue from neonatal male and female littermates. At the cellular level, cardiac fibroblasts obtained from adult and neonatal hearts of both sexes were comparable with respect to the abundance of mRNAs for collagen type I, TGF-β1or cytoskeletal actin. However, DNA synthesis, as measured by [3H]thymidine incorporation, was higher (328%,P< 0.01) in cells from adult female heart compared with that in cells from adult male rat heart. This difference was even more pronounced in cardiac fibroblasts obtained from the newborn female rats (933%,P< 0.001) compared with that in cells obtained from newborn male rat hearts. Together, these findings show that there are sex-related differences in gene expression for most major proteins in heart tissue and that this phenomenon is associated with the post-pubertal period. These findings further suggest that sex-related differential gene expression and DNA synthesis in cardiac cells are due to the regulatory effects of male- and female-specific hormones.