Curtis J F, Reddy N G, Mason R P, Kalyanaraman B, Eling T E
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Arch Biochem Biophys. 1996 Nov 15;335(2):369-76. doi: 10.1006/abbi.1996.0518.
Several recent reports have investigated the possibility that nitric oxide (-NO) can regulate prostaglandin H synthase (PHS) activity. The potential significance of -NO regulation of PHS is considerable, when one considers the numerous important biological processes that are influenced by PHS. In this study, we used microsomal and purified PHS to investigate the direct effect of -NO and -NO-generating compounds on PHS catalytic activity. We found that -NO neither significantly inhibited nor enhanced prostaglandin (PG) formation, despite the fact that -NO stimulated PHS peroxidase activity. We also investigated the effect of -NO and -NO generators on PHS product, protein, and mRNA levels in the RAW264.7 murine macrophage cell line. We found that -NO or -NO generators had little or no effect on PG formation, PHS expression, or PHS mRNA expression in unstimulated RAW264.7 cells. The same results were obtained with macrophages that were stimulated by 18 h pretreatment with lipopolysaccharide, a known inducer of PHS-2 in macrophages. These data clearly indicate that -NO acts as a cosubstrate for PHS peroxidase. However, -NO does not enhance or inhibit either cyclooxygenase activity or expression of PHS in the model systems used in this study.
最近的几份报告研究了一氧化氮（-NO）调节前列腺素H合酶（PHS）活性的可能性。考虑到受PHS影响的众多重要生物学过程，-NO对PHS的调节具有潜在的重要意义。在本研究中，我们使用微粒体和纯化的PHS来研究-NO和产生-NO的化合物对PHS催化活性的直接影响。我们发现，尽管-NO刺激了PHS过氧化物酶活性，但-NO既没有显著抑制也没有增强前列腺素（PG）的形成。我们还研究了-NO和-NO发生器对RAW264.7小鼠巨噬细胞系中PHS产物、蛋白质和mRNA水平的影响。我们发现，在未刺激的RAW264.7细胞中，-NO或-NO发生器对PG形成、PHS表达或PHS mRNA表达几乎没有影响。用脂多糖（一种已知的巨噬细胞中PHS-2诱导剂）预处理18小时刺激的巨噬细胞也得到了相同的结果。这些数据清楚地表明，-NO作为PHS过氧化物酶的共底物。然而，在本研究使用的模型系统中，-NO既不增强也不抑制环氧化酶活性或PHS的表达。
