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Cadmium inhibits proteoglycan and procollagen production by cultured human lung fibroblasts

Chambers, R C; Laurent, G J and Westergren-Thorsson, G LU (1998) In American Journal of Respiratory Cell and Molecular Biology 19(3). p.498-506
Abstract

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 &microM 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... (More)

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 &microM 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.

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keywords
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
in
American Journal of Respiratory Cell and Molecular Biology
volume
19
issue
3
pages
498 - 506
publisher
American Thoracic Society
external identifiers
  • scopus:0032160554
ISSN
1044-1549
DOI
10.1165/ajrcmb.19.3.3242
language
English
LU publication?
yes
id
f220d111-03a8-4dac-a478-ff42938a3272
date added to LUP
2017-06-27 14:07:17
date last changed
2017-07-28 11:01:07
@article{f220d111-03a8-4dac-a478-ff42938a3272,
  abstract     = {<p>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 &lt; 0.01) at 30 &amp;microM 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 &lt; 0.01) and 42 +/- 6% (P &lt; 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.</p>},
  author       = {Chambers, R C and Laurent, G J and Westergren-Thorsson, G},
  issn         = {1044-1549},
  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},
  language     = {eng},
  number       = {3},
  pages        = {498--506},
  publisher    = {American Thoracic Society},
  series       = {American Journal of Respiratory Cell and Molecular Biology},
  title        = {Cadmium inhibits proteoglycan and procollagen production by cultured human lung fibroblasts},
  url          = {http://dx.doi.org/10.1165/ajrcmb.19.3.3242},
  volume       = {19},
  year         = {1998},
}