title: Injury of cell tight junctions and changes of actin level in acute lung injury caused by the perfluoroisobutylene exposure and the role of Myosin light chain kinase.
abstract: OBJECTIVE
  To investigate the injury of cell tight junctions and change in actin level in the alveolus epithelial cells of the lung after perfluoroisobutylene (PFIB) exposure and the role of myosin light chain kinase (MLCK) in the injury.
  
  
  METHODS
  Rats and mice were exposed to a sublethal dose of PFIB. The changes in tight junction zonula occludens-1 (ZO-1), actin and myosin light chain kinase (MLCK) were detected by immunofluorescence at 30 min, 1, 2, 4, 8, 16, 24, 48 and 72 h after PFIB exposure. The role of MLCK was analyzed by lung indices and the actin level.
  
  
  RESULTS
  The normal ZO-1 immunofluorescence density and those after PFIB exposure were 71.63, 39.41, 37.59, 35.71, 33.22, 31.34, 31.61, 24.51, 40.03 and 44.71 respectively, The normal actin immunofluorescence density and those after PFIB exposure were 31.82, 36.46, 36.57, 41.60, 40.95, 35.41, 30.69, 19.96, 29.30 and 33.00 respectively, The normal MLCK immunofluorescence density and those after PFIB exposure were 61.21, 50.87, 48.37, 43.65, 41.96, 35.44, 31.77, 30.85, 33.10 and 38.20 respectively. When the MLCK inhibitor ML-7 was given in advance, pulmonary edema and actin degradation were suppressed.
  
  
  CONCLUSIONS
  At an earlier stage, the increased permeability of the blood-air barrier after PFIB exposure is probably the result of injury of cell tight junctions that acts in concert with later changes in actin, resulting in an increase in permeability. MLCK could be a potential target for novel drug development for relief of acute lung injury.
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Meng
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: He-Mei
authors.initials: HM
authors.lastname: Wang
authors.forename: Ri-Gao
authors.initials: RG
authors.lastname: Ding
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Zhang
authors.forename: Chun-Qian
authors.initials: CQ
authors.lastname: Huang
authors.forename: Jin-Xiu
authors.initials: JX
authors.lastname: Ruan
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D000704:Analysis of Variance; D000818:Animals; D015824:Blood-Air Barrier / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005466:Fluorocarbons / Q000633:toxicity*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009929:Organ Size; D010750:Phosphoproteins / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D062826:Zonula Occludens-1 Protein
chemical_list: D000199:Actins; D005466:Fluorocarbons; D008565:Membrane Proteins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C016648:perfluoroisobutylene; D009219:Myosin-Light-Chain Kinase