tailieunhanh - Báo cáo y học: " The emphysematous lung is abnormally sensitive to TRAIL-mediated apoptosis"

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:" The emphysematous lung is abnormally sensitive to TRAIL-mediated apoptosis. | Morissette et al. Respiratory Research 2011 12 105 http content 12 1 105 RESPIRATORY RESEARCH RESEARCH Open Access The emphysematous lung is abnormally sensitive to TRAIL-mediated apoptosis Mathieu C Morissette Julie Parent and Julie Milot Abstract Background Alveolar apoptosis is increased in the emphysematous lung. However mechanisms involved are not fully understood. Recently we demonstrated that levels of TRAIL receptor 1 and 2 levels of p53 and Bax Bcl-xL ratio were elevated in the lung of subjects with emphysema despite smoking cessation. Thus we postulate that due to chronic pulmonary oxidative stress the emphysematous lung would be abnormally sensitive to TRAIL-mediated apoptosis. Methodology A549 cells were exposed to rTRAIL cigarette smoke extract and or H2O2 prior to caspase-3 activity measurement and annexin V staining assessment. In addition freshly resected lung samples were obtained from non-emphysematous and emphysematous subjects and exposed ex vivo to rTRAIL for up to 18 hours. Lung samples were harvested and levels of active caspase-3 and caspase-8 were measured from tissue lysates. Results Both cigarette smoke extract and H2O2 were able to sensitize A549 cells to TRAIL-mediated apoptosis. Moreover following exposure to rTRAIL caspase-3 and -8 were activated in lung explants from emphysematous subjects while being decreased in lung explants from non-emphysematous subjects. Significance of the study Alveolar sensitivity to TRAIL-mediated apoptosis is strongly increased in the emphysematous lung due to the presence of oxidative stress. This might be a new mechanism leading to increased alveolar apoptosis and persistent alveolar destruction following smoking cessation. Keywords Apoptosis COPD oxidative stress p53 TRAIL Introduction Emphysema largely caused by cigarette smoking is mainly characterized by a loss of alveolar integrity leading to poor gas exchange between the alveolar space and pulmonary capillaries 1 . Moreover