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Remarkably high activities of testicular cytochrome c in destroying reactive oxygen species and in triggering apoptosis

机译:睾丸细胞色素c在破坏活性氧和触发细胞凋亡方面具有很高的活性

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Hydrogen peroxide (H2O2) is the major reactive oxygen species (ROS) produced in sperm. High concentrations of H2O2 in sperm induce nuclear DNA fragmentation and lipid peroxidation and result in cell death. The respiratory chain of the mitochondrion is one of the most productive ROS generating systems in sperm, and thus the destruction of ROS in mitochondria is critical for the cell. It was recently reported that H2O2 generated by the respiratory chain of the mitochondrion can be efficiently destroyed by the cytochrome c-mediated electron-leak pathway where the electron of ferrocytochrome c migrates directly to H2O2 instead of to cytochrome c oxidase. In our studies, we found that mouse testis-specific cytochrome c (T-Cc) can catalyze the reduction of H2O2 three times faster than its counterpart in somatic cells (S-Cc) and that the T-Cc heme has the greater resistance to being degraded by H2O2. Together, these findings strongly imply that T-Cc can protect sperm from the damages caused by H2O2. Moreover, the apoptotic activity of T-Cc is three to five times greater than that of S-Cc in a well established apoptosis measurement system using Xenopus egg extract. The dramatically stronger apoptotic activity of T-Cc might be important for the suicide of male germ cells, considered a physiological mechanism that regulates the number of sperm produced and eliminates those with damaged DNA. Thus, it is very likely that T-Cc has evolved to guarantee the biological integrity of sperm produced in mammalian testis.
机译:过氧化氢(H2O2)是精子中产生的主要活性氧(ROS)。精子中高浓度的H2O2会引起核DNA片段化和脂质过氧化,并导致细胞死亡。线粒体的呼吸链是精子中最有生产力的ROS生成系统之一,因此线粒体中ROS的破坏对于细胞至关重要。最近有报道说,线粒体呼吸链产生的H2O2可以被细胞色素c介导的电子泄漏途径有效地破坏,其中铁细胞色素c的电子直接迁移到H2O2而不是细胞色素c氧化酶。在我们的研究中,我们发现小鼠睾丸特异性细胞色素c(T-Cc)催化H2O2还原的速度是其在体细胞中(S-Cc)的三倍,并且T-Cc血红素对被过氧化氢降解。总之,这些发现强烈暗示T-Cc可以保护精子免受H2O2造成的损害。此外,在使用爪蟾卵提取物的成熟的细胞凋亡测量系统中,T-Cc的凋亡活性是S-Cc的三到五倍。 T-Cc的凋亡活性显着增强,可能对男性生殖细胞的自杀很重要,这被认为是调节精子产生数量并消除DNA受损者的生理机制。因此,很可能已经进化出T-Cc来保证哺乳动物睾丸中产生的精子的生物完整性。

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