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Cadmium inhibits pr...
Cadmium inhibits proteoglycan and procollagen production by cultured human lung fibroblasts
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- Chambers, R C (author)
- University College London
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Laurent, G J (author)
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- Westergren-Thorsson, G (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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(creator_code:org_t)
- American Thoracic Society, 1998
- 1998
- English.
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In: American Journal of Respiratory Cell and Molecular Biology. - : American Thoracic Society. - 1044-1549 .- 1535-4989. ; 19:3, s. 498-506
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Abstract
Subject headings
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- Chronic inhalation of cadmium at the workplace or in cigarette smoke is associated with emphysema, a disease characterized by extensive disruption of lung connective tissue. We have previously shown that cadmium, at noncytotoxic doses, inhibits fibroblast procollagen production in vitro, with maximal inhibitory effects of 69 +/- 6% (P < 0.01) at 30 µM cadmium chloride (CdCl2). In this paper we show that at similar doses, cadmium also inhibits proteoglycan synthesis, with values reduced by between 36 +/- 4% (P < 0.01) and 42 +/- 6% (P < 0.01) for proteoglycans secreted into the culture media and associated with the cell layer, respectively. The greatest inhibition was obtained for the major matrix-associated proteoglycans, versican, decorin, and the large heparan sulfate proteoglycans, with synthesis values reduced by between 60 and 70%. Biglycan and other heparan sulfate proteoglycans were also affected, with synthesis values reduced by between 25 and 45%. In contrast, total protein synthesis was unaffected. Furthermore, effects of cadmium at the protein level were mirrored by reduction in messenger RNA levels for alpha1(I) procollagen, versican, and decorin. These data support the hypothesis that cadmium may play an important role in the pathogenesis of emphysema associated with chronic inhalation of cadmium fumes by inhibiting the production of connective tissue proteins.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Administration, Inhalation
- Cadmium
- Cells, Cultured
- Chondroitin Sulfate Proteoglycans
- Chondroitin Sulfates
- Decorin
- Dermatan Sulfate
- Disaccharides
- Emphysema
- Extracellular Matrix Proteins
- Humans
- Lectins, C-Type
- Lung
- Procollagen
- Protein Synthesis Inhibitors
- Proteoglycans
- RNA, Messenger
- Versicans
- Journal Article
- Research Support, Non-U.S. Gov't
Publication and Content Type
- art (subject category)
- ref (subject category)
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