首页> 外文期刊>American Journal of Physiology >Differential apoptosis-related protein expression, mitochondrial properties, proteolytic enzyme activity, and DNA fragmentation between skeletal muscles.
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Differential apoptosis-related protein expression, mitochondrial properties, proteolytic enzyme activity, and DNA fragmentation between skeletal muscles.

机译:差异凋亡相关的蛋白质表达,线粒体特性,蛋白水解酶活性和骨骼肌之间的DNA片段化。

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Increased skeletal muscle apoptosis has been associated with a number of conditions including aging, disuse, and cardiovascular disease. Skeletal muscle is a complex tissue comprised of several fiber types with unique properties. To date, no report has specifically examined apoptotic differences across muscles or fiber types. Therefore, we measured several apoptotic indices in healthy rat red (RG) and white gastrocnemius (WG) muscle, as well as examined the expression of several key proteins across fiber types in a mixed muscle (mixed gastrocnemius). The protein content of apoptosis-inducing factor (AIF), apoptosis repressor with caspase recruitment domain (ARC), Bax, Bcl-2, cytochrome c, heat shock protein 70 (Hsp70), and second mitochondria-derived activator of caspases (Smac) were significantly (P < 0.05) higher in RG vs. WG muscle. Cytosolic AIF, cytochrome c, and Smac as well as nuclear AIF were also significantly (P < 0.05) higher in RG compared with WG muscle. In addition, ARC protein expression was related to muscle fiber type and found to be highest (P < 0.001) in type I fibers. Similarly, AIF protein expression was differentially expressed across fibers; however, AIF was correlated to oxidative potential (P < 0.001). Caspase-3, -8, and -9 activity, calpain activity, and DNA fragmentation (a hallmark of apoptosis) were also significantly higher (P < 0.05) in RG compared with WG muscle. Furthermore, total muscle reactive oxygen species generation, as well as Ca(2+)-induced permeability transition pore opening and loss of membrane potential in isolated mitochondria were greater in RG muscle. Collectively, these data suggest that a number of apoptosis-related indices differ between muscles and fiber types. Given these findings, muscle and fiber-type differences in apoptotic protein expression, signaling, and susceptibility should be considered when studying cell death processes in skeletal muscle.
机译:骨骼肌细胞凋亡增加与许多疾病相关,包括衰老,废用和心血管疾病。骨骼肌是由几种具有独特特性的纤维类型组成的复杂组织。迄今为止,尚无报告专门检查跨肌肉或纤维类型的凋亡差异。因此,我们测量了健康大鼠红色(RG)和白色腓肠肌(WG)肌肉中的一些细胞凋亡指数,并检查了混合肌(混合腓肠肌)中跨纤维类型的几种关键蛋白的表达。凋亡诱导因子(AIF),具有胱天蛋白酶募集结构域的凋亡抑制因子(ARC),Bax,Bcl-2,细胞色素c,热休克蛋白70(Hsp70)和第二个线粒体衍生的胱天蛋白酶(Smac)的蛋白含量与WG肌肉相比,RG显着增加(P <0.05)。与RG肌肉相比,RG的胞质AIF,细胞色素c和Smac以及核AIF也显着较高(P <0.05)。此外,ARC蛋白表达与肌纤维类型有关,在I型纤维中最高(P <0.001)。同样,AIF蛋白的表达在纤维间差异表达。然而,AIF与氧化电位相关(P <0.001)。与RG肌肉相比,RG的Caspase-3,-8和-9活性,钙蛋白酶活性和DNA片段化(凋亡的标志)也显着更高(P <0.05)。此外,RG肌肉中总的肌肉活性氧物种生成以及Ca(2+)诱导的渗透性过渡孔的开放和孤立线粒体中膜电位的损失更大。总的来说,这些数据表明,肌肉和纤维类型之间许多与凋亡相关的指标不同。鉴于这些发现,在研究骨骼肌细胞死亡过程时,应考虑凋亡蛋白表达,信号传导和敏感性的肌肉和纤维类型差异。

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