Critical role of TXNIP in oxidative stress, DNA damage and retinal pericyte apoptosis under high glucose: implications for diabetic retinopathy.
Critical role of TXNIP in oxidative stress, DNA damage and retinal pericyte apoptosis under high glucose: implications for diabetic retinopathy.
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DOI：
10.1016/j.yexcr.2013.01.012
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发表时间：
2013-04-15
影响因子：
3.7
通讯作者：
Singh LP
中科院分区：
文献类型：
--
作者：
Devi TS;Hosoya K;Terasaki T;Singh LP
糖尿病性视网膜病（DR）的特征是视网膜毛细血管周周的早期丧失和微血管功能障碍。因此，我们在这里假设txnip上调在氧化应激中起着致病作用，而持续的葡萄糖暴露在培养中。低葡萄糖（LG，5.5毫米）或高葡萄糖（Hg，25 mm），有或没有抗氧化剂N-乙酰半胱氨酸（5 mm，NAC），偶氮氨酸（2μM，Azas），TXNIP和TXNIP的抑制剂siRNA（sitxnip3，20 nm）。结果表明，hg在tr-rpct1中增加了TXNIP的表达，这与ROS的产生，蛋白质S-硝基化和促凋亡的caspase-3激活相关。碎片（碱性彗星测定）和MTT存活测定的降低。在慢性高血糖症下，与细胞氧化物应激，DNA损伤和视网膜周围凋亡有关。
Diabetic retinopathy (DR) is characterized by early loss of retinal capillary pericytes and microvascular dysfunction. We recently showed that pro-oxidative stress and pro-apoptotic thioredoxin interacting protein (TXNIP) is significantly up-regulated in rat retinas in experimental diabetes and mediates inflammation and apoptosis. Therefore, we hypothesize here that TXNIP up-regulation in pericyte plays a causative role in oxidative stress and apoptosis under sustained high glucose exposure in culture. We maintained a rat retinal capillary pericyte cell line (TR-rPCT1) for 5 days under low glucose (LG, 5.5 mM) or high glucose (HG, 25 mM) with or without anti-oxidant N-acetylcysteine (5 mM, NAC), Azaseine (2 μM, AzaS), an inhibitor of TXNIP, and TXNIP siRNA (siTXNIP3, 20 nM). The results show that HG increases TXNIP expression in TR-rPCT1, which correlates positively with ROS generation, protein S-nitrosylation, and pro-apoptotic caspase-3 activation. Furthermore, pericyte apoptosis is demonstrated by DNA fragmentation (alkaline comet assay) and a reduction in MTT survival assay. Treatment of TR-rPCT1 with NAC or an inhibition of TXNIP by AzaS or siTXNIP3 each reduces HG-induced ROS, caspase-3 activation and DNA damage demonstrating that TXNIP up-regulation under chronic hyperglycemia is critically involved in cellular oxidative stress, DNA damage and retinal pericyte apoptosis. Thus, TXNIP represents a novel gene and drug target to prevent pericyte loss and progression of DR.
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影响因子：
29
作者：
Lerner AG;Upton JP;Praveen PV;Ghosh R;Nakagawa Y;Igbaria A;Shen S;Nguyen V;Backes BJ;Heiman M;Heintz N;Greengard P;Hui S;Tang Q;Trusina A;Oakes SA;Papa FR
通讯作者：
Papa FR
影响因子：
2
作者：
Ikesugi, Kengo;Mulhern, Michael L.;Shinohara, Toshimichi
通讯作者：
Shinohara, Toshimichi
糖尿病性视网膜病：靶向血管进度。
影响因子：
7.7
作者：
Hammes HP;Feng Y;Pfister F;Brownlee M
通讯作者：
Brownlee M
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.4
作者：
Barber, Alistair J.;Gardner, Thomas W.;Abcouwer, Steven F.
通讯作者：
Abcouwer, Steven F.