title: Adiponectin ameliorates the apoptotic effects of paraquat on alveolar type Ⅱ cells via improvements in mitochondrial function.
abstract: 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.
authors.affiliation: Emergency Medicine Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yarong
authors.initials: Y
authors.lastname: He
authors.affiliation: Emergency Medicine Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Zou
authors.affiliation: Emergency Medicine Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Emergency Medicine Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Hu
authors.affiliation: Emergency Medicine Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yao
authors.affiliation: Emergency Medicine Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yaowen
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Emergency Medicine Department, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610064, P.R. China.
authors.forename: Tun
authors.initials: T
authors.lastname: Yuan
authors.affiliation: Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: Emergency Medicine Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Emergency Medicine Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D052242:Adiponectin / Q000494:pharmacology*; D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology* / Q000633:toxicity; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D052242:Adiponectin; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013481:Superoxides; D000255:Adenosine Triphosphate; D010269:Paraquat