Jiang Ying, Wang Xiaoqin, Hu Daode
Department of Clinical Pharmacology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2017 Apr 13;12:1153-1162. doi: 10.2147/COPD.S130168. eCollection 2017.
The high incidence of chronic obstructive pulmonary disease (COPD), one of the most prevalent diseases worldwide, has attracted growing attention. Cigarette smoking is considered a major contributory factor in the pathogenesis and progression of COPD due to the tremendous oxidative burden that it causes, which induces an oxidant/antioxidant imbalance. Excessive oxidation induced by the excessive generation of mitochondrial reactive oxygen species disturbs the antioxidant systems and plays an important role in triggering and promoting chronic inflammation of airways. Given that mitochondria is one of the main sites of reactive oxygen species production by the oxidative phosphorylation process, oxidative stress may affect mitochondrial function by changing its structure and morphology and by affecting a series of mitochondrial proteins. In particular, PTEN-induced putative kinase 1/Parkin and p62 play critical roles in mitophagy. During the process, the Akt ubiquitin E3 ligase is an important mediator associated with cigarette smoke exposure-induced pulmonary endothelial cell death and dysfunction. Thus, understanding the underlying mechanisms of the signaling pathway may provide important information regarding the therapeutic treatment of COPD by application of alternative PTEN-induced putative kinase 1 targets or ubiquitin E3 ligase.
慢性阻塞性肺疾病（COPD）是全球最常见的疾病之一，其高发病率已引起越来越多的关注。吸烟被认为是COPD发病机制和进展的主要促成因素，因为它会造成巨大的氧化负担，导致氧化/抗氧化失衡。线粒体活性氧过度生成所诱导的过度氧化会扰乱抗氧化系统，并在引发和促进气道慢性炎症中起重要作用。鉴于线粒体是氧化磷酸化过程中产生活性氧的主要部位之一，氧化应激可能通过改变线粒体的结构和形态以及影响一系列线粒体蛋白来影响线粒体功能。特别是，PTEN诱导的假定激酶1/帕金蛋白和p62在线粒体自噬中起关键作用。在此过程中，Akt泛素E3连接酶是与香烟烟雾暴露诱导的肺内皮细胞死亡和功能障碍相关的重要介质。因此，了解该信号通路的潜在机制可能为通过应用替代性PTEN诱导的假定激酶1靶点或泛素E3连接酶来治疗COPD提供重要信息。
