| Abstract |
Summary
It has been previously reported that 5,6,7,S-tetrahydrobiopterin (BH4) modulates HL-60 cell death induced by a nitric oxide (NO) donor, S-nitroso-N-acetyl-D, L-penicillamine (SNAP). In this study, the role of endogenous BH4 was investigated in lipopolysaccharide (LPS)-induced apoptotic cell death. LPS induced an increase of DNA fragmentation and of nitrite and nitrate content (NOx content) in the macrophage- like RAW 264.7 cell line. 2,4-Diamino-6-hydroxypyrimidine (DAHP) , an inhibitor of BH4 synthesis, suppressed both of them. The NOx content of cells treated with LPS and interferon-y was much higher than that of cells treated with LPS alone. However, the degree of apoptotic cell death induced by LPS and interferon-y did not differ significantly from that induced by LPS alone. Further investigation revealed that LPS-induced cell death of RAW264.7 cells was mainly mediated by reactive oxygen species, such as hydrogen peroxide (H2O2). From these data, it was speculated that BH4 might be a modulator in NO-induced apoptosis, in which BH4 involves LPS-induced cell death by its function asa cofactor of inducible NO synthase and it suppresses the cell death mediated by NO and/or H2O2 via an antioxidative activity.
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