Phagocyte-like NADPH oxidase [Nox2] in cellular dysfunction in models of glucolipotoxicity and diabetes.
Phagocyte-like NADPH oxidase [Nox2] in cellular dysfunction in models of glucolipotoxicity and diabetes.
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DOI：
10.1016/j.bcp.2014.01.017
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发表时间：
2014-04-01
影响因子：
5.8
通讯作者：
Kowluru, Renu A.
中科院分区：
文献类型：
--
作者：
Kowluru, Anjaneyulu;Kowluru, Renu A.
细胞内活性氧[ROS]的产生增加与代谢[糖尿病]和神经退行性[阿尔茨海默氏症]疾病的病理学有关。越来越多的证据表明NADPH氧化酶[Nox]是人体细胞ROS的主要来源。在这类酶中，吞噬细胞样Nox [Nox 2]作为诱导细胞损伤的“罪魁祸首”之一受到了严格的审查，最终导致糖尿病及其并发症的发作。Nox 2的功能调节是相当复杂的，由于其膜[gp91phox，p22phox]和胞质[p40phox，p47phox，p67phox和Rac 1]核心，这需要特定的翻译后修饰步骤[磷酸化和脂化]的膜协会。因此，Nox 2的最佳功效取决于这些信号步骤的精确调节，然后将胞质组分易位到膜。有趣的是，许多最近的研究报告了Nox 2的持续激活，ROS衍生的氧化应激，以及在体外和体内模型的糖脂毒性和糖尿病的细胞功能障碍。这些研究采用了多种细胞渗透性肽和药理学抑制剂来阻止在糖脂毒性和糖尿病条件下胰岛β细胞、心肌细胞和视网膜内皮细胞中的Nox 2全酶组装和活化。在此，我们强调现有的证据表明Nox 2是细胞损伤的“触发器”，并确定了我们目前理解的关键差距，需要进一步确认Nox 2作为治疗糖尿病和其他代谢紊乱的潜在治疗靶点的作用。
Increased intracellular generation of reactive oxygen species [ROS] has been implicated in the pathology of metabolic [diabetes] and neurodegenerative [Alzheimer’s] diseases. Accumulating evidence suggests NADPH oxidases [Noxs] as the principal source for cellular ROS in humans. Of this class of enzymes, the phagocyte-like Nox [Nox2] has come under intense scrutiny as one of the “culprits” for the induction of cellular damage culminating in the onset of diabetes and its complications. Functional regulation of Nox2 is fairly complex due to its membranous [gp91phox, p22phox] and cytosolic [p40phox, p47phox, p67phox and Rac1] cores, which require specific post-translational modification steps [phosphorylation and lipidation] for their membrane association. Therefore, optimal efficacy of Nox2 depends upon precise regulation of these signaling steps followed by translocation of the cytosolic components to the membrane. Interestingly, numerous recent studies have reported sustained activation of Nox2, ROS-derived oxidative stress, and cellular dysfunction in in vitro and in vivo models of glucolipotoxicity and diabetes. These investigations employed a variety of cell-permeable peptides and pharmacological inhibitors to impede Nox2 holoenzyme assembly and activation in pancreatic islet β-cells, cardiomyocytes and retinal endothelial cells under conditions of glucolipotoxicity and diabetes. Herein, we highlight the existing evidence to implicate Nox2 as the “trigger” of cellular damage, and identify critical gaps in our current understanding that need to be addressed to further affirm the roles of Nox2 as a potential therapeutic target for the treatment of diabetes and other metabolic disorders.
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影响因子：
6.6
作者：
Frey RS;Ushio-Fukai M;Malik AB
通讯作者：
Malik AB
影响因子：
5.7
作者：
Bid HK;Roberts RD;Manchanda PK;Houghton PJ
通讯作者：
Houghton PJ
影响因子：
7.7
作者：
Kowluru, Anjaneyulu;Veluthakal, Rajakrishnan;Koch, Brandon J.
通讯作者：
Koch, Brandon J.
NADPH 氧化酶氧化还原信号在高血糖诱导的糖尿病视网膜血红素加氧酶-1 表达中的作用。
影响因子：
4.4
作者：
He, Meihua;Pan, Hong;Pu, Mingliang
通讯作者：
Pu, Mingliang
DOI：
10.1073/pnas.1314575110
发表时间：
2013-10-08
影响因子：
11.1
作者：
Du, Yunpeng;Veenstra, Alexander;Kern, Timothy S.
通讯作者：
Kern, Timothy S.