Adiponectin ameliorates the apoptotic effects of paraquat on alveolar type Ⅱ cells via improvements in mitochondrial function.
Adiponectin ameliorates the apoptotic effects of paraquat on alveolar type Ⅱ cells via improvements in mitochondrial function.
复制标题
脂联素通过改善线粒体功能来改善百草枯对 II 型肺泡细胞的凋亡作用
DOI：
10.3892/mmr.2016.5328
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发表时间：
2016-07
影响因子：
3.4
通讯作者：
Cao Y
中科院分区：
文献类型：
--
作者：
He Y;Zou L;Zhou Y;Hu H;Yao R;Jiang Y;Lau WB;Yuan T;Huang W;Zeng Z;Cao Y
已有研究表明，过多活性氧/氮（ROS/RNS）诱导的细胞凋亡是百草枯（PQ）中毒肺上皮损伤的重要特征。然而，pq诱导的线粒体功能障碍（ROS/RNS主要产生的地方）的确切机制仍有待完全阐明。球状脂联素（gAd）作为一种有效的线粒体保护分子，是否调节肺泡II型细胞的线粒体功能以减少pq诱导的ROS/RNS的产生仍有待研究。本研究旨在探讨PQ在肺泡II型细胞线粒体中毒的确切机制，并阐明gAd在PQ诱导的肺上皮损伤中的保护作用。因此，PQ共培养肺泡II型A549细胞24 h，诱导肺上皮损伤，24 h后给予gAd，并将其从损伤细胞中去除，观察到PQ可降低A549细胞活力，使细胞凋亡增加约1.5倍。由ROS/RNS和线粒体功能紊乱引起的氧化/硝化应激可通过O2−增加得到证实。pq中毒的A549细胞中NO的生成和线粒体膜电位的降低（ΔΨ），腺苷5 ' -三磷酸（ATP）含量的降低。gAd治疗显著逆转pq诱导的A549细胞损伤和线粒体功能障碍。gAd的保护作用部分被腺苷5′-单磷酸活化蛋白激酶（AMPK）抑制剂化合物c所取代。结果表明，ΔΨ和ATP含量的降低可能导致PQ诱导的肺上皮线粒体功能障碍，这可能是gAd通过激活AMPK对PQ中毒发挥肺保护作用的新机制。
Previous studies have demonstrated that excessive reactive oxygen/nitrogen species (ROS/RNS)-induced apoptosis is an important feature of the injury to the lung epithelium in paraquat (PQ) poisoning. However the precise mechanisms of PQ-induced dysfunction of the mitochondria, where ROS/RNS are predominantly produced, remain to be fully elucidated. Whether globular adiponectin (gAd), a potent molecule protective to mitochondria, regulates the mitochondrial function of alveolar type II cells to reduce PQ-induced ROS/RNS production remains to be investigated. The current study aimed to investigate the precise mechanisms of PQ poisoning in the mitochondria of alveolar type II cells, and to elucidate the role of gAd in protecting against PQ-induced lung epithelium injury. Therefore, lung epithelial injury was induced by PQ co-culture of alveolar type II A549 cells for 24 h. gAd was administrated to and removed from the injured cells in after 24 h. PQ was observed to reduce cell viability and increase apoptosis by ~1.5 fold in A549 cells. The oxidative/nitrative stress, resulting from ROS/RNS and disordered mitochondrial function were evidenced by increased O2−., NO production and reduced mitochondrial membrane potential (ΔΨ), adenosine 5′-triphosphate (ATP) content in PQ-poisoned A549 cells. gAd treatment significantly reversed the PQ-induced cell injury and mitochondrial dysfunction in A549 cells. The protective effects of gAd were partly abrogated by an adenosine 5′-monophosphate-activated protein kinase (AMPK) inhibitor, compound C. The results suggest that reduced ΔΨ and ATP content may result in PQ-induced mitochondrial dysfunction of the lung epithelium, which constitutes a novel mechanism for gAd exerting pulmonary protection against PQ poisoning via AMPK activation.