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Purine Release, Metabolism, and Signaling in the Inflammatory Response

机译:嘌呤释放,代谢和信号传导在炎症反应中

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摘要

ATP, NAD(+), and nucleic acids are abundant purines that, in addition to having critical intracellular functions, have evolved extracellular roles as danger signals released in response to cell lysis, apoptosis, degranulation, or membrane pore formation. In general ATP and NAD(+) have excitatory and adenosine has anti-inflammatory effects on immune cells. This review focuses on recent advances in our understanding of purine release mechanisms, ectoenzymes that metabolize purines (CD38, CD39, CD73, ENPP1, and ENPP2/autotaxin), and signaling by key P2 purinergic receptors (P2X7, P2Y2, and P2Y12). In addition to metabolizing ATP or NAD(+), some purinergic ectoenzymes metabolize other inflammatory modulators, notably lysophosphatidic acid and cyclicGMP-AMP(cGAMP). Also discussed are extracellular signaling effects of NAD(+) mediated by ADP-ribosylation, and epigenetic effects of intracellular adenosine mediated by modification of S-adenosylmethionine-dependent DNA methylation.
机译:ATP,NAD(+)和核酸是丰富的嘌呤,除了具有临界细胞内功能之外,还在响应于细胞裂解,细胞凋亡,脱粒或膜孔隙形成时进化细胞外作用作为释放的危险信号。 通常,ATP和NAD(+)具有兴奋性,腺苷对免疫细胞具有抗炎作用。 本综述重点介绍了我们对嘌呤释放机制的理解的最新进展,即代谢嘌呤(CD38,CD39,CD73,ENPP1和ENPP2 / AUTOTAXIN)的胞外酶,并通过键P2嘌呤能受体(P2X7,P2Y2和P2Y12)的信号传导。 除了代谢ATP或NAD(+)之外,一些嘌呤能胞外酶除了代谢其他炎症调节剂,特别是透氧磷脂酸和环状蛋白-AMP(CGAMP)。 还讨论的是通过ADP-核糖基化介导的NAD(+)的细胞外信号效应,以及通过改性S-腺苷依赖性DNA甲基化介导的细胞内腺苷的表观遗传效应。

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