Protective Effect of Tempol on Buthionine Sulfoximine-Induced Mitochondrial Impairment in Hippocampal Derived HT22 Cells.
Protective Effect of Tempol on Buthionine Sulfoximine-Induced Mitochondrial Impairment in Hippocampal Derived HT22 Cells.
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DOI：
10.1155/2016/5059043
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发表时间：
2016
影响因子：
--
通讯作者：
Salim S
中科院分区：
文献类型：
--
作者：
Salvi A;Patki G;Khan E;Asghar M;Salim S
利用模拟的海马区永生化细胞系(HT22)的氧化应激模型，我们报道了抗氧化剂丁硫氨酸亚磺胺(BSo，1 mm，14 h)通过抑制谷胱甘肽的合成而诱导氧化应激，而不对细胞的存活率和形态产生不利影响。与赋形剂处理的对照细胞相比，硫代巴比妥酸处理还显著降低了HT22细胞的超氧化物歧化酶活性(p<；0.001)和总抗氧化能力(p<；0.05)。抗氧化剂坦普尔，一种被认为是超氧化物歧化酶模拟物的哌啶氮氧化物，逆转了BSO诱导的SOD活性下降(p<；0.01)，并增加了BSO诱导的总抗氧化能力的下降(p<；0.05)。有趣的是，与赋形剂处理的对照细胞相比，BSO处理显著降低了线粒体的耗氧量(p<；0.05)，降低了线粒体膜电位(p<；0.05)，并降低了ATP的产生(p<；0.05)，这些共同表明线粒体受损。抗氧化剂Tempoll治疗减轻了线粒体损伤的所有三个指标。我们推测，BSO诱导的氧化应激导致HT22细胞线粒体损伤，而temol可能通过增加SOD活性和提高抗氧化能力来保护细胞免受BSO诱导的线粒体损伤。总之，本研究提供了一个有趣的海马细胞氧化应激模拟，这将成为研究线粒体功能的一个很好的模型。
Using a simulated oxidative stress model of hippocampus-derived immortalized cell line (HT22), we report that prooxidant buthionine sulfoximine (BSO, 1 mM, 14 h), without adversely affecting cell viability or morphology, induced oxidative stress by inhibiting glutathione synthesis. BSO treatment also significantly reduced superoxide dismutase (SOD) activity (p < 0.05) and significantly lowered total antioxidant capacity (p < 0.001) in HT22 cells when compared to vehicle treated control cells. Antioxidant tempol, a piperidine nitroxide considered a SOD mimetic, reversed BSO-induced decline in SOD activity (p < 0.01) and also increased BSO-induced decline in total antioxidant capacity (p < 0.05). Interestingly, BSO treatment significantly reduced mitochondrial oxygen consumption (p < 0.05), decreased mitochondrial membrane potential (p < 0.05), and lowered ATP production (p < 0.05) when compared to vehicle treated control cells, collectively indicative of mitochondrial impairment. Antioxidant tempol treatment mitigated all three indicators of mitochondrial impairment. We postulate that BSO-induced oxidative stress in HT22 cells caused mitochondrial impairment, and tempol by increasing SOD activity and improving antioxidant capacity presumably protected the cells from BSO-induced mitochondrial impairment. In conclusion, present study provides an interesting simulation of oxidative stress in hippocampal cells, which will serve as an excellent model to study mitochondrial functions.