Evidence for increased de novo synthesis of NAD in immune-activated RAW264.7 macrophages:: A self-protective mechanism?
Evidence for increased de novo synthesis of NAD in immune-activated RAW264.7 macrophages:: A self-protective mechanism?
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DOI：
10.1006/abbi.1999.1381
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发表时间：
1999-12-01
影响因子：
3.9
通讯作者：
Kapoor, V
中科院分区：
文献类型：
--
作者：
Grant, RS;Passey, R;Kapoor, V
母体吡啶核苷酸NAD是通过犬尿氨酸途径氧化色氨酸催化剂的终产物。吲哚胺2，3-双加氧酶是该途径的限速酶，由促炎细胞因子干扰素-γ诱导。本研究的目的是研究干扰素-γ处理对小鼠巨噬细胞系RAW 264.7中细胞内NAD浓度的影响。γ-干扰素作用24 h后，细胞内NAD浓度显著升高，多聚腺苷酸抑制剂可显著增强γ-干扰素介导的NAD浓度升高。（ADP-核糖）聚合酶或一氧化氮合酶或用合成糖皮质激素地塞米松处理后，NAD产生依赖于培养基中色氨酸的存在和功能性吲哚胺2，3-双加氧酶活性。与先前的研究一致，在用干扰素-γ激活后，在这些细胞中观察到一氧化氮产生的显著增加。这些结果首次提供了证据，即在用干扰素-γ刺激的RAW 264.7巨噬细胞中，由色氨酸从头合成NAD伴随着自由基产生而增加，NAD生物合成的这种增加可以为核修复酶聚（ADP-核糖）聚合酶提供改善的底物供应，从而有助于DNA修复和细胞活力。(C)北京：科学出版社.
The parent pyridine nucleotide NAD is the end product of oxidative tryptophan catabolism via the kynurenine pathway. Indoleamine 2,3-dioxygenase, the rate-limiting enzyme for this pathway, is induced by the proinflammatory cytokine interferon-gamma, The aim of this study was to investigate the effect of interferon-gamma treatment on intracellular NAD concentration in the murine macrophage cell line, RAW 264.7. A significant increase in intracellular NAD concentration was observed following 24 h exposure to interferon-gamma, This cytokine-mediated increase in NAD concentration was markedly enhanced by the inhibition of poly(ADP-ribose) polymerase or nitric oxide synthase or following treatment with the synthetic glucocorticoid dexamethasone, NAD production was dependent on both the presence of tryptophan in the culture medium and on functional indoleamine 2,3-dioxygenase activity. In agreement with previous studies a marked increase in nitric oxide production was observed in these cells following activation with interferon-gamma, These results provide evidence for the first time that de novo synthesis of NAD from tryptophan is increased concomitantly with free radical production in RAW 264.7 macrophages stimulated with interferon-gamma, This increase in NAD biosynthesis may provide an improved supply of substrate to the nuclear repair enzyme poly(ADP-ribose) polymerase assisting in DNA repair and hence cell viability. (C) 1999 Academic Press.