Convergence of nitric oxide and lipid signaling: anti-inflammatory nitro-fatty acids.
Convergence of nitric oxide and lipid signaling: anti-inflammatory nitro-fatty acids.
复制标题
DOI：
10.1016/j.freeradbiomed.2008.11.021
复制
发表时间：
2009-04-15
影响因子：
7.4
通讯作者：
Freeman, Bruce A.
中科院分区：
文献类型：
--
作者：
Baker, Paul R. S.;Schopfer, Francisco J.;O'Donnell, Valerie B.;Freeman, Bruce A.
信号传导介质一氧化氮（·NO）和氧化脂质，曾经被视为通过离散和独立的途径传递代谢和炎症信息，现在被认为是免疫反应和代谢稳态的相互依赖的调节剂。这两类介体之间的相互作用导致介体合成的相互控制，这受到局部化学环境的强烈影响。这两种途径之间的关系超出了·NO和类花生酸形成的共同调节，通过不饱和脂肪酸的硝化产生硝基衍生物（NO2-FA）而收敛。这些多能信号分子在体内产生作为对氧化性炎症条件的适应性应答，并且主要表现出抗炎信号反应。NO2-FA的这些作用是多种多样的，这些物种作为·NO的潜在化学储备，与细胞亲核试剂反应，以后修饰蛋白质的结构，功能和定位。在这方面，这些物质作为过氧化物酶体增殖物激活受体γ的有效内源性配体。这些信号传导机制的功能后果已在多个模型系统中显示，包括抑制血小板和中性粒细胞功能、诱导血红素加氧酶-1、抑制单核细胞中LPS诱导的细胞因子释放、增加脂肪细胞中的胰岛素敏感性和葡萄糖摄取以及松弛预收缩的大鼠主动脉段。这些观察结果进一步推动了NO2-FA信号传导和代谢机制的体外和体内研究，突出了这类分子作为抗炎药物候选物的治疗潜力。
The signaling mediators nitric oxide (·NO) and oxidized lipids, once viewed to transduce metabolic and inflammatory information via discrete and independent pathways, are now appreciated as interdependent regulators of immune response and metabolic homeostasis. The interactions between these two classes of mediators result in reciprocal control of mediator sythesis that is strongly influenced by the local chemical environment. The relationship between the two pathways extends beyond co-regulation of ·NO and eicosanoid formation to converge via the nitration of unsaturated fatty acids to yield nitro derivatives (NO2-FA). These pluripotent signaling molecules are generated in vivo as an adaptive response to oxidative inflammatory conditions and manifest predominantly anti-inflammatory signaling reactions. These actions of NO2-FA are diverse, with these species serving as a potential chemical reserve of ·NO, reacting with cellular nucleophiles to post-translationally modify protein structure, function and localization. In this regard these species act as potent endogenous ligands for peroxisome proliferator activated receptor γ. Functional consequences of these signaling mechanisms have been shown in multiple model systems, including the inhibition of platelet and neutrophil functions, induction of heme oxygenase-1, inhibition of LPS-induced cytokine release in monocytes, increased insulin sensitivity and glucose uptake in adipocytes and relaxation of pre-constricted rat aortic segments. These observations have propelled further in vitro and in vivo studies of mechanisms of NO2-FA signaling and metabolism, highlighting the therapeutic potential of this class of molecules as anti-inflammatory drug candidates.
登录
查看更多内容
影响因子：
15.9
作者：
Bell-Parikh, LC;Ide, T;FitzGerald, GA
通讯作者：
FitzGerald, GA
DOI：
10.1073/pnas.0402587101
发表时间：
2004-08-10
影响因子：
11.1
作者：
Baker, PRS;Schopfer, FJ;Freeman, BA
通讯作者：
Freeman, BA
影响因子：
4.8
作者：
Baker, Laura M. S.;Baker, Paul R. S.;Freeman, Bruce A.
通讯作者：
Freeman, Bruce A.
影响因子：
4.4
作者：
Bannenberg, GL;Chiang, N;Serhan, CN
通讯作者：
Serhan, CN
影响因子：
4.8
作者：
Baker, PRS;Lin, YM;Freeman, BA
通讯作者：
Freeman, BA