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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.

AbstractOBJECTIVES:
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.
AuthorsGe Meng, Jian Zhao, He-Mei Wang, Ri-Gao Ding, Xian-Cheng Zhang, Chun-Qian Huang, Jin-Xiu Ruan
JournalJournal of occupational health (J Occup Health) Vol. 53 Issue 4 Pg. 250-7 ( 2011) ISSN: 1348-9585 [Electronic] Australia
PMID21670563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Actins
  • Fluorocarbons
  • Membrane Proteins
  • Phosphoproteins
  • Tjp1 protein, mouse
  • Tjp1 protein, rat
  • Zonula Occludens-1 Protein
  • perfluoroisobutylene
  • Myosin-Light-Chain Kinase
Topics
  • Actins (drug effects, metabolism)
  • Acute Lung Injury (chemically induced, metabolism, pathology)
  • Analysis of Variance
  • Animals
  • Blood-Air Barrier (drug effects, metabolism)
  • Epithelial Cells (drug effects, metabolism)
  • Fluorocarbons (toxicity)
  • Male
  • Membrane Proteins (metabolism)
  • Mice
  • Myosin-Light-Chain Kinase (antagonists & inhibitors, metabolism)
  • Organ Size
  • Phosphoproteins (metabolism)
  • Pulmonary Edema (chemically induced, pathology)
  • Rats
  • Rats, Wistar
  • Tight Junctions (drug effects, metabolism)
  • Time Factors
  • Zonula Occludens-1 Protein

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