Reduction of glutathione is associated with growth restriction and enlargement of bovine pulmonary artery endothelial cells produced by transforming growth factor-beta 1.
In addition to inhibiting proliferation and causing enlargement of bovine pulmonary artery endothelial cells in culture, porcine platelet transforming growth factor-beta 1 (TGF-beta 1) (2 ng/ml) lowered glutathione (GSH) of these cells by 48% after 96 h in culture when GSH levels were normalized for cell counts. This lowering of cellular GSH was more marked when corrections were made for approximated cell volume. TGF-beta 1 produced only moderate inhibition of pulmonary artery smooth muscle cell proliferation and did not significantly reduce the GSH content of these cells, even at concentrations as high as 8 ng/ml. Elevation of GSH of endothelial cells above control levels by 0.05 mM diethylmaleate or 1 mM cystine prevented the inhibition of cellular proliferation produced by TGF-beta 1. Lowering cellular GSH levels by approximately 85% for 24 to 72 h with 0.01 mM buthionine sulfoximine (BSO) in the absence of TGF-beta 1 had no effect on proliferation or size of the endothelial cells. However, 0.01 mM BSO potentiated the inhibitory effect of TGF-beta 1 on endothelial cell proliferation and in combination with TGF-beta 1 caused cellular detachment at low endothelial cell densities. Thus, although TGF-beta 1 lowers the level of endothelial cellular GSH, this in itself does not appear to account for the inhibition of proliferation and enlargement of these cells produced by TGF-beta 1. Rather, the combination of another unidentified action of TGF-beta 1 in the presence of reduced cellular GSH likely accounts for these effects.
White
A C
AC
Department of Medicine, New England Medical Center, Boston, Massachusetts 02111.
Das
S K
SK
Fanburg
B L
BL
D000818:Animals; D019328:Buthionine Sulfoximine; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003553:Cystine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D007700:Kinetics; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D011651:Pulmonary Artery; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D008717:Methionine Sulfoximine; D003553:Cystine; D019328:Buthionine Sulfoximine; D005978:Glutathione