首页> 外文期刊>Endothelium: Journal of endothelial cell research >Essential role of NOXA1 in generation of reactive oxygen species induced by oxidized low-density lipoprotein in human vascular endothelial cells.
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Essential role of NOXA1 in generation of reactive oxygen species induced by oxidized low-density lipoprotein in human vascular endothelial cells.

机译:NOXA1在人血管内皮细胞中被氧化的低密度脂蛋白诱导的活性氧生成中的重要作用。

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摘要

Oxidative stress induced by superoxide plays an important role in pathogenesis of cardiovascular diseases. NAD(P)H oxidase is a principal enzymatic origin for superoxide in vasculature. Recently, novel homologues of cytosolic components of NAD(P)H oxidase, Nox organizer 1 (NOXO1) and Nox activator 1 (NOXA1), are identified. On the other hand, oxidized low-density lipoprotein (ox-LDL) generates reactive oxygen species (ROS) in endothelial cells via lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). In the present investigation, the authors examined the expression, the regulation, and the role of NOXA1 in the generation of ROS in endothelial cells. The expression of NOXA1 was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). Dihydroethidium method showed that ox-LDL and angiotensin II increased the generation of intracellular ROS. Once the expression of p22(phox) or NOXA1 was suppressed by siRNA, the generation of ROS induced by ox-LDL and angiotensin II were potently decreased. Moreover, the expression of NOXA1 was increased by ox-LDL in a time-and dose-dependent manner. In conclusion, endothelial NOXA1 plays an essential role in generation of ROS. Ox-LDL not only increased the generation of ROS via LOX-1, but also enhanced the expression of NOXA1 in endothelial cells. NOXA1 is likely a key player that links ox-LDL with the activation of endothelial NAD(P)H oxidase.
机译:超氧化物诱导的氧化应激在心血管疾病的发病机理中起重要作用。 NAD(P)H氧化酶是脉管系统中超氧化物的主要酶促来源。最近,鉴定了NAD(P)H氧化酶,NOx组织者1(NOXO1)和Nox激活剂1(NOXA1)的胞质成分的新同源物。另一方面,氧化的低密度脂蛋白(ox-LDL)通过凝集素样氧化的低密度脂蛋白受体1(LOX-1)在内皮细胞中产生活性氧(ROS)。在本研究中,作者检查了NOXA1在内皮细胞中ROS生成中的表达,调控和作用。通过逆转录聚合酶链反应(RT-PCR)证实了NOXA1的表达。二氢乙啶法显示ox-LDL和血管紧张素II增加了细胞内ROS的生成。一旦siRNA抑制了p22(phox)或NOXA1的表达,ox-LDL和血管紧张素II诱导的ROS的产生就会大大减少。此外,ox-LDL以时间和剂量依赖性方式增加了NOXA1的表达。总之,内皮型NOXA1在ROS的产生中起着至关重要的作用。 Ox-LDL不仅通过LOX-1增加了ROS的生成,而且还增强了内皮细胞中NOXA1的表达。 NOXA1可能是将ox-LDL与内皮NAD(P)H氧化酶激活联系在一起的关键参与者。

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