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.