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首页> 外文期刊>Biological chemistry >Switch from actin alpha 1 to alpha 2 expression and upregulation of biomarkers for pressure overload and cardiac hypertrophy in taurine-deficient mouse heart
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Switch from actin alpha 1 to alpha 2 expression and upregulation of biomarkers for pressure overload and cardiac hypertrophy in taurine-deficient mouse heart

机译:从肌动蛋白alpha 1转换为alpha 2的表达以及牛磺酸缺乏小鼠心脏中压力超负荷和心脏肥大的生物标志物的上调

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摘要

Taurine is the most abundant free amino acid in heart muscle and protects against heart failure. In the present study, the consequences of hereditary taurine deficiency on cardiac gene expression were examined in 2-and 15-16-month-old taurine transporter knockout (taut(-/-)) mice using a mouse-specific DNA microarray. This oligonucleotide-based microarray contains probes for 251 genes with relevance for heart function. Of these, 163 probes exhibited a reproducible hybridization signal and were analyzed. alpha-Actin type 1 mRNA levels were 70% lower in the heart of young and older taut(-/-) mice compared to wild-type controls. Interestingly, the hearts of taut(-/-) mice showed a switch from alpha-actin 1 to alpha-actin 2 expression, as confirmed by real-time PCR and Western blot analysis. In addition, mRNA levels of biomarkers for pressure overload and hypertension were upregulated in taut(-/-) hearts, i.e., atrial natriuretic factor (+848%), brain natriuretic peptide (+90%), cardiac ankyrin repeat protein (+118%), and procollagen 1a1, 1a2 and 3a1 (+40% at least). These results point to a stress situation in the heart of taut(-/-) mice under laboratory conditions, and it can be speculated that taut(-/-) hearts may be even more susceptible to failure in the wild when under exogenous stress.
机译:牛磺酸是心肌中最丰富的游离氨基酸,可预防心力衰竭。在本研究中,使用小鼠特异性DNA微阵列在2和15-16个月大的牛磺酸转运蛋白敲除(taut(-/-))小鼠中检查了遗传性牛磺酸缺乏对心脏基因表达的影响。这种基于寡核苷酸的微阵列包含与心脏功能相关的251个基因的探针。在这些探针中,有163个探针显示出可再现的杂交信号并进行了分析。与野生型对照组相比,年轻和年长的taut(-/-)小鼠心脏中的α-肌动蛋白1型mRNA水平降低了70%。有趣的是,taut(-/-)小鼠的心脏显示从α-肌动蛋白1转换为α-肌动蛋白2的表达,这已通过实时PCR和Western blot分析证实。此外,taut(-/-)心脏中用于压力超负荷和高血压的生物标志物的mRNA水平上调,即心房利钠因子(+ 848%),脑利钠肽(+ 90%),心脏锚蛋白重复蛋白(+118) %)和胶原蛋白1a1、1a2和3a1(至少+ 40%)。这些结果表明,在实验室条件下,taut(-/-)小鼠的心脏处于应激状态,可以推测,在外源压力下,taut(-/-)的心脏在野外可能更容易衰竭。

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