Document Detail


Chrysotile asbestos causes AEC apoptosis via the caspase activation in vitro and in vivo.
MedLine Citation:
PMID:  18300051     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To determine whether alveolar epithelial cell (AEC) apoptosis via caspase activation is involved in asbestos-induced lung injury, we examined apoptosis, caspase-3 and-9 activation using chrysotile asbestos exposure models in vitro and in vivo. Apoptotic cells were assessed in A549 cells with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method after 48 hours exposure of chrysotile asbestos (5 to 100 ug/cm2). Asbestos exposure induced a dose-dependent increase of apoptotic cells, and both pretreatment with Z-LEHD-FMK (caspase-3 inhibitor) or Z-DEMK-FMK (caspase-9 inhibitor) significantly suppressed asbestos-induced apoptosis. Expression of cleaved caspase-3 and-9 increased significantly from 18 to at least 48 hours after asbestos exposure. In vivo study, either 1 or 2 mg of chrysotile asbestos were administered into rat lungs intratracheally, and the lungs were obtained 3 days, 1 and 2 weeks, 1, 3 and 6 months after the administration. Asbestos exposure increased the number of apoptotic cells and the activation of cleaved caspase-3 and -9 most at 3 days in a dose dependent manner, and continued to increase them until at least 6 months after asbestos exposure. Apoptotic cells and cleaved caspase-3 and -9 positive cells were mainly observed in AECs. These findings suggest that AEC apoptosis via caspase-3 and -9 activation is involved in asbestos-induced lung injury.
Authors:
Takashi Kido; Yasuo Morimoto; Etsuko Asonuma; Kazuhiro Yatera; Akira Ogami; Takako Oyabu; Isamu Tanaka; Masamitsu Kido
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Inhalation toxicology     Volume:  20     ISSN:  1091-7691     ISO Abbreviation:  Inhal Toxicol     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-26     Completed Date:  2008-03-13     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  8910739     Medline TA:  Inhal Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  339-47     Citation Subset:  IM    
Affiliation:
Department of Respiratory Disease, University of Occupational and Environmental Health, Fukuoka, Japan. t-kido@med.uoeh-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Air Pollutants / toxicity*
Animals
Apoptosis / drug effects*
Asbestos, Serpentine / toxicity*
Blotting, Western
Caspase 3 / antagonists & inhibitors,  metabolism*
Caspase 9 / antagonists & inhibitors,  metabolism*
Cell Count
Cell Line, Transformed
Cells, Cultured
Dose-Response Relationship, Drug
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Fluorescent Antibody Technique, Direct
Granuloma, Foreign-Body / chemically induced,  pathology
Humans
Immunoenzyme Techniques
In Situ Nick-End Labeling
Intubation, Intratracheal
Lung / drug effects,  enzymology,  pathology
Male
Particle Size
Pulmonary Alveoli / drug effects*,  enzymology,  pathology
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
0/Air Pollutants; 0/Asbestos, Serpentine; 0/Enzyme Inhibitors; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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