Signaling of reactive oxygen and nitrogen species in Diabetes mellitus.
Signaling of reactive oxygen and nitrogen species in Diabetes mellitus.
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DOI：
10.4161/oxim.3.6.14415
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发表时间：
2010-11
影响因子：
--
通讯作者：
Afanas'ev I
中科院分区：
文献类型：
--
作者：
Afanas'ev I
活性氧（ROS）超氧化物和过氧化氢以及活性氮（RNS）一氧化氮和过氧亚硝酸盐生理信号功能紊乱是1型和2型糖尿病的重要特征。目前已知细胞的高血糖状况与主要由线粒体和NADPH氧化酶产生的ROS水平升高有关。已经确定，在正常生理条件下，ROS 会刺激许多酶级联反应，但高血糖会导致 ROS 过量产生和 ROS 信号通路失调，从而引发糖尿病的发展。另一方面，RNS 信号传导的失调基本上导致 NO 形成的减少以及随后的破坏性疾病。在目前的工作中，我们将考虑蛋白激酶 C 和 B (Akt/B)、磷脂酰肌醇 3′-激酶 (PI3-激酶)、细胞外信号调节激酶 1/2 (ERK1/2) 等催化的酶/基因调节过程中 ROS 和 RNS 信号传导的病理变化。此外，我们将讨论几个 ROS 调节基因和接头蛋白（例如 p66shc、FOXO3a 和 Sirt2）的特别重要作用。低和高 ROS 水平对糖尿病的影响也将被考虑。因此，通过抗氧化剂和自由基清除剂调节糖尿病中有害的ROS水平必定是治疗该疾病的一种有前途的治疗方法，然而，由于传统的抗氧化维生素E和C无法与超氧化物和过氧化氢相互作用，因此应深入研究新的自由基清除剂，例如类黄酮、醌和超氧化物歧化酶（SOD）的合成模拟物。
Disorder of physiological signaling functions of reactive oxygen species(ROS) superoxide and hydrogen peroxide and reactive nitrogen species (RNS) nitric oxide and peroxynitrite is an important feature of diabetes mellitus type 1 and type 2. It is now known that hyperglycemic conditions of cells are associated with the enhanced levels of ROS mainly generated by mitochondria and NADPH oxidase. It has been established that ROS stimulate many enzymatic cascades under normal physiological conditions, but hyperglycemia causes ROS overproduction and the deregulation of ROS signaling pathways initiating the development of diabetes mellitus. On the other hand the deregulation of RNS signaling leads basically to a decrease in NO formation with subsequent damaging disorders. In the present work we will consider the pathological changes of ROS and RNS signaling in enzyme/gene regulated processes catalyzed by protein kinases C and B (Akt/B), phosphatidylinositol 3′-kinase (PI3-kinase), extracellular signal-regulated kinase 1/2 (ERK1/2) and some others. Furthermore we will discuss a particularly important role of several ROS-regulated genes and adapter proteins such as the p66shc, FOXO3a and Sirt2. The effects of low and high ROS levels in diabetes will be also considered. Thus the regulation of damaging ROS levels in diabetes by antioxidants and free radical scavengers must be one of promising treatment of this disease, however, because of the inability of traditionalantioxidative vitamin E and C to interact with superoxide and hydrogen peroxide,new free radical scavengers such as flavonoids, quinones and synthetic mimetics of superoxide dismutase (SOD) should be intensively studied.
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影响因子：
7.4
作者：
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通讯作者：
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DOI：
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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