title: Proteasome inhibition attenuates lung injury induced by intestinal ischemia reperfusion in rats.
abstract: The aim of this study is to investigate the role of proteasome in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion (I/R) by examining the effect of the proteasome inhibitor lactacystin on neutrophil infiltration, intracellular adhesion molecule-1 (ICAM-1) expression and nuclear factor kappa B (NF-kappaB) activation. Thirty-two Wistar rats were divided into (1) control, (2) intestinal I/R, (3) 0.2 mg/kg lactacystin pretreated, and (4) 0.6 mg/kg lactacystin pretreated groups (n=8). Injuries in lung and intestine were induced by intestinal I/R, and were characterized by histological edema, hemorrhage and infiltration of inflammatory cells. The results showed a significant increase in serum creatine kinase B (CK-B) and lung water content in intestine and lung injuries. As compared with the control group, the myeloperoxidase (MPO) activity in intestine and lung as well as the serum TNF-alpha level increased significantly in intestinal I/R group. Simultaneously, expression of ICAM-1 and NF-kappaB p65 was also observed in the I/R group. Pre-treatment with lactacystin markedly reduced 20S proteasome activity in circulating white blood cells and ameliorated intestine and lung injuries. These results demonstrated that the proteasome participates in the pathogenesis of lung injury induced by intestinal I/R. Lactacystin as a proteasome inhibitor can prevent this kind of injury by decreasing ICAM-1 and TNF-alpha production via the inhibition of NF-kappaB activation.
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China. txfdl@hotmail.com
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Tian
authors.forename: Xue-Song
authors.initials: XS
authors.lastname: Zhang
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Li
authors.forename: Zheng-Zheng
authors.initials: ZZ
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Wang
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Yao
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism; D052276:Creatine Kinase, BB Form / Q000097:blood; D007422:Intestines / Q000098:blood supply* / Q000473:pathology; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000097:blood; D061988:Proteasome Inhibitors; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D061988:Proteasome Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D052276:Creatine Kinase, BB Form; D046988:Proteasome Endopeptidase Complex