OGG1 Involvement in High Glucose-Mediated Enhancement of Bupivacaine-Induced Oxidative DNA Damage in SH-SY5Y Cells.
OGG1 Involvement in High Glucose-Mediated Enhancement of Bupivacaine-Induced Oxidative DNA Damage in SH-SY5Y Cells.
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OGG1 参与高葡萄糖介导的 SH-SY5Y 细胞中布比卡因诱导的氧化 DNA 损伤的增强
DOI：
10.1155/2015/683197
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发表时间：
2015
影响因子：
--
通讯作者：
Xu SY
中科院分区：
文献类型：
--
作者：
Liu ZJ;Zhao W;Zhang QG;Li L;Lai LY;Jiang S;Xu SY
高血压可抑制8-oxoG-DNA糖基化酶（OGG 1）的表达，OGG 1是DNA氧化损伤的关键修复酶之一。高血糖对OGG 1表达的影响在响应局部麻醉剂诱导的DNA损伤是未知的。本研究旨在确定高葡萄糖是否抑制OGG 1表达并通过活性氧（ROS）消除布比卡因诱导的DNA损伤。在用1.5mM布比卡因处理SH-SY 5 Y细胞24小时之前，将SH-SY 5 Y细胞用或不用50 mM葡萄糖培养8天。通过定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹法测定OGG 1表达。用氧化还原敏感的荧光染料DCFH-DA检测ROS，用8-oxodG免疫染色和彗星试验检测DNA损伤。与对照培养条件相比，暴露于高糖的细胞中OGG 1表达受到抑制，伴随着ROS产生的增加和更严重的DNA损伤，布比卡因进一步加剧了这些变化。用抗氧化剂N-乙酰-L-半胱氨酸（NAC）治疗可防止高糖和布比卡因介导的ROS产生增加，并恢复OGG 1的功能表达，从而减弱高糖介导的布比卡因神经毒性加重。我们的研究结果表明，患有糖尿病的受试者可能会遇到更多的不利影响布比卡因使用。
Hyperglycemia can inhibit expression of the 8-oxoG-DNA glycosylase (OGG1) which is one of the key repair enzymes for DNA oxidative damage. The effect of hyperglycemia on OGG1 expression in response to local anesthetics-induced DNA damage is unknown. This study was designed to determine whether high glucose inhibits OGG1 expression and aggravates bupivacaine-induced DNA damage via reactive oxygen species (ROS). SH-SY5Y cells were cultured with or without 50 mM glucose for 8 days before they were treated with 1.5 mM bupivacaine for 24 h. OGG1 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. ROS was estimated using the redox-sensitive fluorescent dye DCFH-DA. DNA damage was investigated with immunostaining for 8-oxodG and comet assays. OGG1 expression was inhibited in cells exposed to high glucose with concomitant increase in ROS production and more severe DNA damage as compared to control culture conditions, and these changes were further exacerbated by bupivacaine. Treatment with the antioxidant N-acetyl-L-cysteine (NAC) prevented high glucose and bupivacaine mediated increase in ROS production and restored functional expression of OGG1, which lead to attenuated high glucose-mediated exacerbation of bupivacaine neurotoxicity. Our findings indicate that subjects with diabetes may experience more detrimental effects following bupivacaine use.
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DOI：
10.1016/j.mrfmmm.2014.04.002
发表时间：
2014-05
影响因子：
2.3
作者：
Inturi, Swetha;Tewari-Singh, Neera;Agarwal, Chapla;White, Carl W.;Agarwal, Rajesh
通讯作者：
Agarwal, Rajesh
影响因子：
5.3
作者：
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通讯作者：
Boldogh, Istvan
影响因子：
2.9
作者：
Kilarkaje, Narayana;Al-Bader, Maie M.
通讯作者：
Al-Bader, Maie M.
影响因子：
5.7
作者：
Hebl, James R.;Kopp, Sandra L.;Horlocker, Terese T.
通讯作者：
Horlocker, Terese T.
影响因子：
3.6
作者：
So, Eui Young;Ouchi, Toru
通讯作者：
Ouchi, Toru