Hypoxia induces cell damage via oxidative stress in retinal epithelial cells
Hypoxia induces cell damage via oxidative stress in retinal epithelial cells
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DOI：
10.3109/10715762.2013.867484
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发表时间：
2014-03-01
影响因子：
3.3
通讯作者：
Valacchi, G.
中科院分区：
文献类型：
--
作者：
Cervellati, F.;Cervellati, C.;Valacchi, G.
视网膜疾病(RD)，包括糖尿病视网膜病变，是工业化国家最重要的眼病之一。RD的特点是血管生成异常，伴随细胞增殖和凋亡的增加。缺氧可能是该病发病机制的触发因素之一。细胞S低氧反应系统的一个关键调控成分是低氧诱导因子1α(HIF-1α)。已经证明，在体外，也可以通过氯化钴(CoCl2)诱导HIF-1α的表达，导致细胞内出现类缺氧状态。在这项研究中，我们研究了CoCl2对人视网膜上皮细胞(HRPE)的影响，hRPE是血-视网膜屏障的组成部分，目的是确定氧化应激在化学缺氧诱导的视网膜上皮细胞损伤中的可能作用。我们的数据表明，CoCl2处理能够诱导HIF-1α的表达，这与活性氧(ROS)的形成以及脂质8-异前列腺素和4-羟基壬烯醛(4-HNE)蛋白加合物水平的增加是平行的。此外，我们还观察到氧化还原敏感的转录因子核因子-kappaB(NFkB)被CoCl2激活，这可以解释血管内皮生长因子(VEGF)水平的升高。死亡细胞数量的增加似乎与细胞凋亡过程有关。综上所述，这些证据表明，低氧诱导的氧化应激可能通过刺激RD的新生血管生成和细胞凋亡两个关键事件参与RD的发生发展。
Retinal diseases (RD), including diabetic retinopathy, are among the most important eye diseases in industrialized countries. RD is characterized by abnormal angiogenesis associated with an increase in cell proliferation and apoptosis. Hypoxia could be one of the triggers of the pathogenic mechanism of this disease. A key regulatory component of the cell ' s hypoxia response system is hypoxia-inducible factor 1 alpha (HIF-1 alpha). It has been demonstrated that the induction of HIF-1 alpha expression can be also achieved in vitro by exposure with cobalt chloride (CoCl2), leading to an intracellular hypoxia-like state. In this study we have investigated the eff ects of CoCl2 on human retinal epithelium cells (hRPE), which are an integral part of the blood - retinal barrier, with the aim to determine the possible role of oxidative stress in chemical hypoxia-induced damage in retinal epithelial cells. Our data showed that CoCl2 treatment is able to induce HIF-1 alpha expression, that parallels with the formation of reactive oxygen species ( ROS) and the increase of lipid 8-isoprostanes and 4-hydroxynonenal (4-HNE) protein adducts levels. In addition we observed the activation of the redox-sensitive transcription factor nuclear factor-kappaB (NFkB) by CoCl2 which can explain the increased levels of vascular endothelial growth factor (VEGF). The increased number of dead cells seems to be related to an apoptotic process. Taken together these evidences suggest that oxidative stress induced by hypoxia might be involved in RD development through the stimulation of two key-events of RD such as neo-angiogenesis and apoptosis.