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First, we examined the effects of various chemical NO-donors on the cell damage in HL-60 cells. The most potent of these was S-nitroso-N-acetyl- penicillamine (SNAP). The effect of 5,6,7,8-tetrahydrobiopterin (BH 4 ) on HL-60 cell damage induced by SNAP was investigated. Analysis of electrophoresis of DNA fragmentation induced by SNAP indicated that the cell damage was caused via apoptosis. This phenomenon was observed as early as 5 hr after the treatment with 500 mM SNAP. Apoptosis observed at an early time, 5 hr post-treatment with SNAP, was inhibited by BH 4  . However, BH 4  significantly increased cell death observed at a later time, 20 hr after the treatment. These results suggest that BH 4  may be involved in modulating the cytotoxicity, including cell death, mediated by NO.

Effects of Tetrahydrobiopterin (BH 4 ) on S-Nitroso-N-acetyl-D,Lpenicillamine (SNAP)-Induced HL-60 Cell Death