Two pathways of the nitric oxide-induced cytotoxycal action.
Nitric oxide is a diffusible messenger with multiple biological functions. We show here that NO-generating compound, S-nitrosoglutathione (GSNO) induces apoptosis in human chondrocytes and causes necrosis-like cell death in human epithelial CaOv cell line. Pretreatment of chondrocytes with low-dose GSNO or with gamma-interferon enhances their tolerance 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 human chondrocytes possess specific and inducible mechanism preventing cell killing by nitric oxide.