Modulation of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) induced HL-60 cell death by tetrahydrobiopterin.
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.
Kojima
S
S
Research Institute for Biological Sciences, Science University of Tokyo, Chiba, Japan. Kjima@mail.rs.noda.sut.ac.jp
Nimura
K
K
Komatsu
H
H
Taguchi
T
T
Iizuka
H
H
D017209:Apoptosis / Q000187:drug effects*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D053938:DNA Fragmentation; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine
D001708:Biopterins; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D007770:L-Lactate Dehydrogenase; C003402:sapropterin; D010396:Penicillamine