Role of zinc in pulmonary endothelial cell response to oxidative stress

Croix, and Bruce R. Pitt. Role of zinc in pulmonary endo-thelial cell response to oxidative stress. Am J Physiol Lung Cell Mol Physiol 281: L243–L249, 2001.—Although zinc is a well-known inhibitor of apoptosis, it may contribute to oxidative stress-induced necrosis. We noted that N,N,N9,N9-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN;.10 mM), a zinc chelator, quenched fluorescence of the zinc-specific fluorophore Zinquin and resulted in an increase in spon-taneous apoptosis in cultured sheep pulmonary artery endothelial cells (SPAECs). Addition of exogenous zinc (in the presence of pyrithione, a zinc ionophore) to the medium of SPAECs caused an increase in Zinquin fluorescence and was associated with a concentration-dependent increase in necrotic cell death. Exposure of SPAECs to TPEN (10 mM) resulted in enhanced apoptosis after lipopolysaccharide o