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Modulation of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) induced HL-60 cell death by tetrahydrobiopterin
S Kojima1, K Nimura, H Komatsu
1Research Institute for Biological Sciences, Science University of Tokyo, Chiba, Japan. Kjima@mail.rs.noda.sut.ac.jp
Abstract:
The effect of 5,6,7,8-tetrahydrobiopterin (BPH4) on HL-60 cell damage induced by a nitric oxide (NO) donor, S-nitroso-N-acetyl-penicillamine (SNAP), was investigated. The activity of lactate dehydrogenase (LDH), a marker of cell damage, was elevated dose- and time-dependently after treatment with SNAP. The cells underwent apoptosis, as judged from the characteristic morphological findings and the electrophoretic ladder pattern of DNA fragments. Apoptosis observed at an early time, 5 hours post-treatment with SNAP, was inhibited by BPH4. However, BPH4 significantly increased cell death observed at a later time, 20 hours after the treatment. These results suggest that BPH4 may be involved in modulating the cytotoxicity, including cell death, mediated by NO.