Tian Liang, Liu Guangfan, Kang Ziqi, Yan Peishi
Department of Intelligent Animal Husbandry and Environmental Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Biomedicines. 2022 Jan 13;10(1):165. doi: 10.3390/biomedicines10010165.
The aim of this investigation was to evaluate the role of MARK4 in the regulation of oxidative stress and mitochondrial dysfunction in pig placental trophoblasts and analyze the signaling pathways involved. In this study, we found that enhanced MARK4 contributed to augmented oxidative stress in pig trophoblasts, as evidenced by decreased total antioxidant capacity (TAC); higher production of reactive oxygen species (ROS); elevated protein carbonylation; and reduced SOD, CAT, and GSH-PX activities. Further analyses revealed MARK4 impaired mitochondrial oxidative respiration in cultured trophoblasts, which was associated with reduced ATP content, decreased mitochondrial membrane potential, lower mitochondrial Complexes I and III activities, and down-regulated protein contents of subunits of complexes I, II, and V. At same time, mitochondrial biogenesis and structure were negatively altered by elevated MARK4. By antioxidant treatment with vitamin E (VE), oxidative stress along with impaired mitochondrial function induced by enhanced MARK4 were blocked. Furthermore, we found activation of AMPK signaling prevented MARK4 from blocking mitochondrial biogenesis and function in pig trophoblast cells. Finally, we demonstrated that the IKKα/NF-κB signal pathway was involved in MARK4 activated oxidative stress and mitochondrial dysfunction. Thus, these data suggest that MARK4 promotes oxidative stress and mitochondrial injury in porcine placental trophoblasts and can contribute to the developing of knowledge of pathological processes leading to mitochondrial dysfunction associated with excessive back-fat in the pig placenta and to the obesity-associated pregnant syndrome.
本研究旨在评估MARK4在猪胎盘滋养层细胞氧化应激调节和线粒体功能障碍中的作用，并分析其中涉及的信号通路。在本研究中，我们发现增强的MARK4会导致猪滋养层细胞氧化应激增加，总抗氧化能力（TAC）降低、活性氧（ROS）生成增加、蛋白质羰基化水平升高以及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-PX）活性降低均证明了这一点。进一步分析表明，MARK4损害了培养的滋养层细胞中的线粒体氧化呼吸，这与ATP含量降低、线粒体膜电位下降、线粒体复合物I和III活性降低以及复合物I、II和V亚基的蛋白质含量下调有关。同时，MARK4升高会对线粒体生物发生和结构产生负面影响。通过用维生素E（VE）进行抗氧化处理，可阻断由增强的MARK4诱导的氧化应激以及线粒体功能受损。此外，我们发现激活AMPK信号可防止MARK4阻断猪滋养层细胞中的线粒体生物发生和功能。最后，我们证明IKKα/NF-κB信号通路参与了MARK4激活的氧化应激和线粒体功能障碍。因此，这些数据表明，MARK4促进猪胎盘滋养层细胞中的氧化应激和线粒体损伤，并有助于加深对导致猪胎盘过度背膘相关线粒体功能障碍的病理过程以及肥胖相关妊娠综合征的认识。
