Abstract
Several studies indicate that active oxygen species play an important role in the development of pulmonary disease (asbestosis and silicosis) after exposure to mineral dust. The present study was conducted to determine if inhaled fibrogenic minerals induced changes in gene expression and activities of antioxidant enzymes (AOE) in rat lung. Two different fibrogenic minerals were compared, crocidolite, an amphibole asbestos fiber, and cristobalite, a crystalline silicon dioxide particle. Steady-state mRNA levels, immunoreactive protein, and activities of selected AOE were measured in lungs 1-10 days after initiation of exposure and at 14 days after cessation of a 10-day exposure period. Exposure to asbestos resulted in significant increases in steady-state mRNA levels of manganese-containing superoxide dismutase (MnSOD) at 3 and 9 days and of glutathione peroxidase at 6 and 9 days. An increase in steady-state mRNA levels of copper, zinc-containing superoxide dismutase (CuZnSOD), was observed at 6 days. Exposure to asbestos also resulted in overall increased enzyme activities of catalase, glutathione peroxidase and total superoxide dismutase in lung. In contrast, silica caused a dramatic increase in steady-state levels of MnSOD mRNA at all time periods and an increase in glutathione peroxidase mRNA levels at 9 days. Activities of AOE remained unchanged in silica-exposed lungs. In both models, increases in gene expression of MnSOD correlated with increased amounts of MnSOD immunoreactive protein in lung and the pattern and extent of inflammation. These data indicate that the profiles of AOE are dissimilar during the development of experimental asbestosis or silicosis and suggest different mechanisms of lung defense in response to these minerals.
Highlights
Several studies indicate that active oxygen species initial lung response to asbestos and silica [1,2,3]
The patterns of steady-state mRNA expression of antioxidant enzymes (AOE) in lung were different after inhalationof silica
Profiles of AOEgene expression and activity in lungs were distinct after inhalation of asbestos or silica, an observation suggestingdifferent patterns of lung defense and/or repair intheseinhalation models
Summary
0 1992b y The American Society for Biochemistry and Molecular Biology, Inc. Vol 267,No.. Activities of total superoxide dismutase, catalase, and glutathione peroxidase were increased in rat lung after exposure ogy, University of Vermont, College of Medicine, Burlington, V T 05405. The abbreviations used are: AOS, active oxygen species; AM, alveolar macrophage; AOE, antioxidant enzymes: BAL, bronchoalveolar lavage;CuZnSOD,copper zinc-superoxidedismutase; MnSOD, manganese-superoxide dismutase; PEG, polyethylene glycol; PMN, polymorphonuclear leukocyte; TNF, tumor necrosis factor; TEMED, to asbestos [23]. Lung in EnzyAmnteisoxidant study was conducted to determine if inhalation of cristobalite, homogenized in phosphate buffer (0.05 M, 1 mM EDTA, pH 7.8) on a crystalline silicon dioxide particle (defined as a 3:1 ratio), induced changes in steady-state mRNA levels, immunoreactive proteina,nd activities of certain AOE (MnSOD, copper zinc-SOD [CuZnSOD], glutathione peroxia t the highest speed) and centrifuged at 14,000 rpm (4 "C). Antioxidant Enzyme Activities-The left lungs were minced and with steady-state mRNA levels of MnSOD
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