Document Detail

Reduction of endothelial cell related TGFbeta activity by thiols.
MedLine Citation:
PMID:  10365774     Owner:  NLM     Status:  MEDLINE    
Transforming growth factor beta (TGFbeta) may play an important role in diseases characterized by pulmonary fibrosis. We have previously demonstrated that thiols inhibit the pro-oxidant effects of TGFbeta1 in bovine pulmonary artery endothelial cells (BPAEC). To help define the mechanism of this observation we have examined the effect of reduced (GSH) and oxidized (GSSG) glutathione, N-acetyl cysteine (NAC) and cysteine (CYS) on the biological activity of a) TGFbeta released by bovine pulmonary artery endothelial cells (BPAEC) into culture medium, and b) commercially available porcine platelet TGFbeta1. The biological activity of TGFbeta (following activation) released into the medium from cultured BPAEC was significantly reduced when the cells were cultured in the presence of 10 mM GSH or 10 mM NAC for 24 h (10 mM GSH: 85.7 +/- 50 pg/ml/10(6) cells and 10 mM NAC: 127.3 +/- 35 pg/ml/10(6) cells, compared with control: 541 +/- 8.9 pg/ml/10(6) cells; p < 0.05). Thiols (10 mM GSH, 10 mM NAC and 5 mM cysteine), added directly to cell-free conditioned medium or to a commercially available preparation of porcine platelet TGFbeta1 for 6-24 h had a similar inhibitory effect on the biological activity of TGFbeta and altered the structure of porcine platelet TGFbeta1 as determined by mass spectroscopy. These thiols failed to reduce the expression of TGFbeta mRNA in BPAEC as measured by a competitive polymerase chain reaction assay. Incubating endothelial cells or cell-free conditioned medium with GSSG did not alter the biological activity of TGFbeta. Lower doses of thiols (0.1-1 mM), that we have shown inhibit the antiproliferative and pro-oxidant effects of exogenous TGFbeta1 on BPAEC, had no direct effect on TGFbeta bioactivity. In summary, thiols are capable of reducing the effects of TGFbeta in biological systems through a direct effect on the TGFbeta molecule. However, this action appears to be dose-dependent, and at low doses (0.1-1 mM) thiols may also inhibit the actions of exogenous TGFbeta1 in cell culture through a mechanism involving the cellular redox status.
A C White; E K Maloney; S L Lee; J J Lanzillo; B L Fanburg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Endothelium : journal of endothelial cell research     Volume:  6     ISSN:  1062-3329     ISO Abbreviation:  Endothelium     Publication Date:  1999  
Date Detail:
Created Date:  1999-08-03     Completed Date:  1999-08-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9412590     Medline TA:  Endothelium     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  231-9     Citation Subset:  IM    
Department of Medicine/Tupper Research Institute, New England Medical Center/Tufts University School of Medicine, Boston, MA 02111, USA.
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MeSH Terms
Acetylcysteine / pharmacology
Cells, Cultured
Culture Media, Conditioned
Cysteine / pharmacology
Dose-Response Relationship, Drug
Endothelium, Vascular / cytology,  metabolism*
Glutathione / metabolism,  pharmacology
Glutathione Disulfide / metabolism,  pharmacology
Pulmonary Artery / cytology
Sulfhydryl Compounds / metabolism*,  pharmacology
Transforming Growth Factor beta / genetics,  metabolism*,  secretion
Grant Support
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Sulfhydryl Compounds; 0/Transforming Growth Factor beta; 27025-41-8/Glutathione Disulfide; 52-90-4/Cysteine; 616-91-1/Acetylcysteine; 70-18-8/Glutathione

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