GRP78, HSP72/73, and cJun stress protein levels in lung epithelial cells exposed to asbestos, cadmium, or H2O2.
Timblin CR; Janssen YM; Goldberg JL; Mossman BT
Free Radic Biol Med 1998 Mar; 24(4):632-642
Occupational exposure to crocidolite asbestos is associated with the development of nonmalignant and malignant pulmonary disease. Considerable evidence indicates that the mechanisms of asbestos-induced toxicity involve the production of active oxygen species (AOS). Production of AOS in excess of cellular defenses creates an environment of oxidative stress and stimulates the expression of a number of different genes whose products may be involved in mediating responses from oxidant injury. To further investigate the mechanisms of asbestos-induced pathogenicity, we have examined by Western blot analyses the induction of the stress response proteins GRP78 and HSP72/73 in rat lung epithelial cells (RLE) exposed to crocidolite asbestos. In comparative studies, we also examined GRP78, HSP72/73, and cJun expression in RLE cells exposed to equitoxic concentrations of cadmium chloride (CdCl2) and hydrogen peroxide (H2O2). Our results demonstrate that asbestos and H2O2 do not alter GRP78 or HSP72/73 protein levels in RLE cells, but do increase levels of cJun protein. Increases by asbestos and H2O2 were not accompanied by alterations in cellular glutathione levels in this cell type, but asbestos caused elevations in protein levels of manganese-containing superoxide dismutase (MnSOD), an indirect indicator of oxidant stress. In contrast, exposure of cells to CdCl2 led to no changes in MnSOD protein levels, but increases in GRP78, HSP72/73, and cJun proteins as well as significant increases in oxidized and reduced thiol pools. Results suggest that environmental agents causing oxidative injury to lung epithelium elicit different patterns of stress responses.
Lung-cells; Proteins; Asbestosis; Asbestos-dust; Asbestos-fibers; Cadmium-dust; Cadmium-compounds; Occupational-exposure; Occupational-diseases; Diseases; Pulmonary-system-disorders; Free-radicals
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Free Radical Biology and Medicine
University of Vermont & St Agric College, Burlington, Vermont