2 PATHWAYS OF THE NITRIC OXIDE-INDUCED CYTOTOXICAL ACTION

Nitric oxide is a diffusible messenger with multiple biological functi ons. We show here that NO-generating compound, S-nitrosoglutathione (G SNO) induces apoptosis in human chondrocytes and causes necrosis-like cell death in human epithelial CaOv cell line. Pretreatment of chondro cytes with low-dose GSNO or with gamma-interferon enhances their toler ance to the second high-concentration GSNO exposure. On the contrary, in CaOv cells low-dose GSNO pretreatment diminishes the resistance and increases cytolysis at the second GSNO exposure. We conclude that hum an chondrocytes possess specific and inducible mechanism preventing ce ll killing by nitric oxide.