TAILIEUCHUNG - Báo cáo y học: " AMP-activated protein kinase deficiency reduces ozone-induced lung injury and oxidative stress in mice"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài:" AMP-activated protein kinase deficiency reduces ozone-induced lung injury and oxidative stress in mice. | Hulo et al. Respiratory Research 2011 12 64 http content 12 1 64 RESPIRATORY RESEARCH RESEARCH Open Access AMP-activated protein kinase deficiency reduces ozone-induced lung injury and oxidative stress in mice CÁp-sí-tAn I_Il I I z 1 2 f I_I A I A I I z 1 3 f c ỉ I s I 1 4 f I r- I I z . I I I r D A V V A 1 2 f Drm At ỉ z I I z .4-5 6 7 f sebastien HUio Helene liesset Sieve Lancel Jean J Louis tame Denon Viollet Annie Sobaszek1 2f and Remi Nevière1 4 f Abstract Background Acute ozone exposure causes lung oxidative stress and inflammation leading to lung injury. At least one mechanism underlying the lung toxicity of ozone involves excessive production of reactive oxygen and nitrogen intermediates such as peroxynitrite. In addition and beyond its major prooxidant properties peroxynitrite may nitrate tyrosine residues altering phosphorylation of many protein kinases involved in cell signalling. It was recently proposed that peroxynitrite activates 5 -AMP-activated kinase AMPK which regulates metabolic pathways and the response to cell stress. AMPK activation as a consequence of ozone exposure has not been previously evaluated. First we tested whether acute ozone exposure in mice would impair alveolar fluid clearance increase lung tissue peroxynitrite production and activate AMPK. Second we tested whether loss of AMP-activated protein kinase alpha1 subunit in mouse would prevent enhanced oxidative stress and lung injury induced by ozone exposure. Methods Control and AMPKal deficient mice were exposed to ozone at a concentration of ppm for 3 h in glass cages. Evaluation was performed 24 h after ozone exposure. Alveolar fluid clearance AFC was evaluated using fluorescein isothiocyanate tagged albumin. Differential cell counts total protein levels cytokine concentrations myeloperoxidase activity and markers of oxidative stress . malondialdehyde and peroxynitrite were determined in bronchoalveolar lavage BAL and lung homogenates LH . Levels

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