Sun Yi, Zhang Wen-Jia, Zhao Xin, Yuan Ren-Pei, Jiang Hui, Pu Xiao-Ping
State Key Laboratory of Natural and Biomimetic DrugsDepartment of Molecular and Cellular PharmacologySchool of Pharmaceutical Science, Peking University, Beijing, People's Republic of ChinaDepartment of AndrologyPeking University Third Hospital, Beijing 100191, People's Republic of ChinaState Key Laboratory of Natural and Biomimetic DrugsDepartment of Molecular and Cellular PharmacologySchool of Pharmaceutical Science, Peking University, Beijing, People's Republic of ChinaDepartment of AndrologyPeking University Third Hospital, Beijing 100191, People's Republic of China.
State Key Laboratory of Natural and Biomimetic DrugsDepartment of Molecular and Cellular PharmacologySchool of Pharmaceutical Science, Peking University, Beijing, People's Republic of ChinaDepartment of AndrologyPeking University Third Hospital, Beijing 100191, People's Republic of China.
Reproduction. 2014 Sep;148(3):249-57. doi: 10.1530/REP-14-0222. Epub 2014 Jun 11.
PARK7 (DJ1) is a multifunctional oxidative stress response protein that protects cells against reactive oxygen species (ROS) and mitochondrial damage. PARK7 defects are known to cause various physiological dysfunctions, including infertility. Asthenozoospermia (AS), i.e. low-motile spermatozoa in the ejaculate, is a common cause of human male infertility. In this study, we found that downregulation of PARK7 resulted in increased levels of lipid peroxide and ROS, decreased mitochondrial membrane potential, and reduced mitochondrial complex I enzyme activity in the spermatozoa from AS patients. Furthermore, it was observed that PARK7 was translocated into the mitochondria of damaged spermatozoa in AS. Finally, we examined the oxidative state of PARK7 and the results demonstrated the enhancement of oxidation, expressed by increased sulfonic acid residues, the highest form of oxidation, as the sperm motility decreased. Taken together, these results revealed that PARK7 deficiency may increase the oxidative stress damage to spermatozoa. Our present findings open new avenues of therapeutic intervention targeting PARK7 for the treatment of AS.
PARK7（DJ1）是一种多功能氧化应激反应蛋白，可保护细胞免受活性氧（ROS）和线粒体损伤。已知PARK7缺陷会导致各种生理功能障碍，包括不育。弱精子症（AS），即射精中精子活力低下，是人类男性不育的常见原因。在本研究中，我们发现PARK7的下调导致AS患者精子中脂质过氧化物和ROS水平升高、线粒体膜电位降低以及线粒体复合物I酶活性降低。此外，观察到PARK7易位到AS中受损精子的线粒体中。最后，我们检测了PARK7的氧化状态，结果表明随着精子活力下降，磺酸残基增加所表示的氧化增强，磺酸残基是最高形式的氧化。综上所述，这些结果表明PARK7缺乏可能会增加对精子的氧化应激损伤。我们目前的研究结果为针对PARK7治疗AS开辟了新的治疗干预途径。
