Radio-protective effect and mechanism of 4-Acetamido-2,2,6,6- tetramethylpiperidin-1-oxyl in HUVEC cells.
Radio-protective effect and mechanism of 4-Acetamido-2,2,6,6- tetramethylpiperidin-1-oxyl in HUVEC cells.
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4-Acetamido-2,2,6,6-tetramethylpiperidin-1-oxyl对HUVEC细胞的辐射防护作用及机制
DOI：
10.1186/s12199-017-0616-9
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发表时间：
2017-03-24
影响因子：
4.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Wang F;Gao P;Guo L;Meng P;Fan Y;Chen Y;Lin Y;Guo G;Ding G;Wang H
为了寻找毒性更小、更有效的辐射防护剂，研究了水溶性氮氧化物-乙酰胺-坦波尔(AA-Tempoll)对人脐静脉内皮细胞(HUVEC)的辐射防护作用。方法采用克隆存活实验研究AA-Temol对体外培养的HUVEC细胞的辐射防护作用。采用Annexin V/碘化丙啶染色流式细胞术检测AA-Tempoll的抗细胞凋亡作用。通过检测Bax、Bcl2、P53和caspase-3的表达，探讨AA-Tempoll抗X射线诱导的HUVEC细胞凋亡的分子机制。结果照射前1h用AA-坦普尔处理内皮细胞集落，可显著提高集落存活率(p <； 0.05)。这说明AA-TEMPOL对照射后的人脐静脉内皮细胞具有有效的辐射防护作用，使细胞凋亡率从8GyX射线照射后的20.1mmo1± 1.3%减少到12.2 mmo1± 0.9%(1.0 /L −1 AA-Templ)。提示1.0mM AA-TEMPOL可显著阻断照射后人脐静脉内皮细胞半胱氨酸天冬氨酸氨基转移酶-3活性的升高(P <； .01)，导致Bax、P53蛋白表达下调，Bcl2蛋白表达上调。与8GyX射线照射的人脐静脉内皮细胞相比，AA-坦普尔可显著降低细胞内丙二醛活性(P <； 0.0 1)，升高细胞内 水平(P <；GSH0.0 5)。结论AA-坦普尔是一种潜在的抗辐射损伤药物。
ObjectivesTo search for more effective radiation protectors with minimal toxicity, a water-soluble nitroxides Acetamido-Tempol (AA-Tempol) was evaluated for potential radioprotective properties in HUVEC cells (Human Umbilical Vein Endothelial cell line).MethodsTo study the anti-radiation effect of AA-Tempol in cell culture, the viability of irradiated HUVEC cells using a clonogenic survival assay was examined. The anti-apoptosis effects of AA-Tempol using Annexin V/propidium iodide staining in a flow cytometry assay was also evaluated. To elucidate the molecular mechanism of the anti-apoptosis effect of AA-Tempol against X-radiation induced HUVEC cell apoptosis, the expression of Bax, Bcl-2 and p53 and caspase-3 were examined. The changes in the level of malondialdehyde (MDA) and glutathione (GSH) in HUVEC cells after X-radiation were also investigated.ResultsPretreatment of the HUVEC cells colony with AA-Tempol 1 h before X-radiation significantly increased the colony survival (p < 0.05) compared with the cells without pretreatment. This demonstrates that AA-Tempol provides an effective radiation protection in the irradiated HUVEC cells, thus reducing apoptosis from 20.1 ± 1.3% in 8 Gy X-radiated cells to 12.2 ± 0.9% (1.0 mmol/L−1 AA-Tempol) in AA-Tempo pretreated HUVEC cells. This implies that 1.0 mM AA-Tempol treatment significantly block the increase of caspase-3 activity in radiated HUVEC cells (P < 0.01), causing down-regulation in expressions of Bax and P53 and up-regulation in the expression of Bcl-2. Pretreatment with AA-Tempol also decreased the MDA activities (P < 0.01) and increase the GSH level (P < 0.05) in HUVEC cells compared to the 8Gy X-radiated cells without pretreatment.ConclusionsThese observations indicate that AA-Tempol is a potential therapeutic agent against the radiation damage.
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DOI：
10.1073/pnas.1110358108
发表时间：
2011-08-09
影响因子：
11.1
作者：
Croker, Ben A.;O'Donnell, Joanne A.;Roberts, Andrew W.
通讯作者：
Roberts, Andrew W.
影响因子：
6.1
作者：
Greaves, ED;Manz, A
通讯作者：
Manz, A
影响因子：
4.3
作者：
Guo, Juan;Zhang, Yanjun;Guo, Guozhen
通讯作者：
Guo, Guozhen
影响因子：
7.9
作者：
Jagetia, GC;Baliga, MS;Kamath, MS
通讯作者：
Kamath, MS
影响因子：
3.5
作者：
Belikova, Natalia A.;Jiang, Jianfei;Stoyanovsky, Detcho A.;Glumac, Ashley;Bayir, Huelya;Greenberger, Joel S.;Kagan, Valerian E.
通讯作者：
Kagan, Valerian E.