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首页> 外文期刊>Cellular Physiology and Biochemistry >Transgenic overexpression of heart-specific adenine nucleotide translocase 1 positively affects contractile function in cardiomyocytes
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Transgenic overexpression of heart-specific adenine nucleotide translocase 1 positively affects contractile function in cardiomyocytes

机译：心脏特异性腺嘌呤核苷酸转座酶1的转基因过表达积极影响心肌细胞的收缩功能

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Background/Aims: The adenine nucleotide translocase (ANT) exchanges ATP and ADP over the inner mitochondrial membrane, supplying the cells with energy. Interestingly, myocardial ANT1 overexpression preserves cardiac structure and function under pathophysiological conditions. To ascertain whether the contractile system is directly affected by increased ANT1 expression, we analyzed cell morphology, contraction and relaxation parameters of ANT1 transgenic (ANT1-TG) cardiomyocytes, myofibrillar protein expression, and Ca~(2+) handling in ANT1-TG rat hearts. Results: ANT1-TG cardiomyoycytes displayed an elevation in cell volume (52.6±12.0%; p<0.0001) in comparison to wildtype (WT) cells. Concurrently, contractile function in ANT1-TG cells was significantly increased, measured by a decline in time to peak contraction (TTP) and RT50, the time from peak contraction to 50% relaxation, during stimulation with 0.5, 1, and 2 Hz. Quantification of myofibrillar proteins exhibited a marked increase in total cardiac myosin heavy chain (51.8±12.8%) (p<0.03), beta myosin heavy chain (22.9±5.0%; p<0.03), actin (23.8±8.8%; p<0.05), and troponin I (51.5±13.7%; p<0.01). Regarding intracellular Ca~(2+) handling, ANT1-TGs revealed a significant elevation in sarcoplasmic reticulum (SR) Ca~(2+) ATPase (SERCA2a) protein level (22.2±4.7%; p<0.01) associated with increased Ca~(2+) uptake into the SR (34%; p<0.01). Moreover, the plasmalemmal Ca~(2+) ATPase (PMCA) indicated advanced protein expression (23.8±4.8%; p<0.01), whereas the protein amount of the Na+/Ca~(2+) exchanger was not altered in ANT1 overexpressing hearts. Conclusion: These data reveal a close association of elevated mitochondrial ATP/ADP transportation via ANT1 with increased contractile function. Furthermore, the ANT1-TGs exhibit an elevation in SR Ca~(2+) transport that contributes to increased cardiac work, which may protect the heart under pathophysiological conditions.
机译：背景/目的：腺嘌呤核苷酸转位酶（ANT）在线粒体内膜上交换ATP和ADP，为细胞提供能量。有趣的是，心肌ANT1的过表达可以在病理生理条件下保留心脏的结构和功能。为了确定收缩系统是否直接受ANT1表达增加的影响，我们分析了ANT1-TG大鼠ANT1转基因（ANT1-TG）心肌细胞的细胞形态，收缩和松弛参数，肌原纤维蛋白表达以及Ca〜（2+）处理心。结果：与野生型（WT）细胞相比，ANT1-TG心肌细胞的细胞体积增加（52.6±12.0％; p <0.0001）。同时，在以0.5、1、2 Hz刺激期间，通过峰收缩时间（TTP）和RT50（从峰收缩到松弛50％的时间）的减少，可以测量ANT1-TG细胞的收缩功能。肌原纤维蛋白的定量显示总心肌肌球蛋白重链（51.8±12.8％）（p <0.03），β肌球蛋白重链（22.9±5.0％; p <0.03），肌动蛋白（23.8±8.8％; p < 0.05）和肌钙蛋白I（51.5±13.7％; p <0.01）。关于细胞内Ca〜（2+）的处理，ANT1-TGs显示肌浆网（SR）Ca〜（2+）ATPase（SERCA2a）蛋白水平显着升高（22.2±4.7％; p <0.01） （2+）被SR吸收（34％; p <0.01）。此外，质膜Ca〜（2+）ATPase（PMCA）表示蛋白质表达提前（23.8±4.8％; p <0.01），而在ANT1过表达中Na + / Ca〜（2+）交换子的蛋白质量没有改变。心。结论：这些数据表明线粒体ATP / ADP通过ANT1转运的增加与收缩功能的增强密切相关。此外，ANT1-TGs的SR Ca〜（2+）转运升高，这有助于增加心脏的功，可以在病理生理条件下保护心脏。

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