Assessment of Protective Role of Multifunctional Dopamine Agonist D-512 Against Oxidative Stress Produced by Depletion of Glutathione in PC12 Cells: Implication in Neuroprotective Therapy for Parkinson's Disease.
Assessment of Protective Role of Multifunctional Dopamine Agonist D-512 Against Oxidative Stress Produced by Depletion of Glutathione in PC12 Cells: Implication in Neuroprotective Therapy for Parkinson's Disease.
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DOI：
10.1007/s12640-015-9548-6
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发表时间：
2015-11
影响因子：
3.7
通讯作者：
Dutta AK
中科院分区：
文献类型：
--
作者：
Voshavar C;Shah M;Xu L;Dutta AK
氧化应激与帕金森病（PD）的进展密切相关。细胞质谷胱甘肽水平的耗尽是氧化应激的指征之一，其在疾病过程的早期阶段发生在PD患者的黑质中。已显示谷胱甘肽耗竭导致线粒体复合物I的抑制，从而影响线粒体功能，导致通过活性氧物质的产生的氧化应激。研究了D2/D3受体激动剂D-512对谷胱甘肽合成关键酶抑制剂丁硫酰亚胺（BSO）和神经毒素6-羟基多巴胺（6-OHDA）诱导的多巴胺能PC 12细胞的保护作用。D-512能够针对BSO/6-OHDA介导的谷胱甘肽耗竭恢复谷胱甘肽水平。D-512还显示出对BSO和6-OHDA联合处理诱导的PC 12细胞毒性的显著神经保护作用。此外，D-512能够在6-OHDA处理后恢复磷酸化细胞外信号调节激酶和磷酸化Jun N-末端激酶水平，这为通过调节丝裂原活化蛋白激酶进行神经保护的可能作用机制提供了证据。我们进一步证明了D-512对PC 12细胞中BSO和6-OHDA产生的氧化损伤的神经保护作用。
Oxidative stress has been strongly implicated in the progression of Parkinson’s disease (PD). Depletion of cytoplasmic glutathione levels is one of the indications of oxidative stress, which occur in the substantia nigra of PD patients at an early stage of the disease process. It has been shown that glutathione depletion causes the inhibition of mitochondrial complex I, thus affecting mitochondrial function leading to oxidative stress via production of reactive oxygen species. Studies were carried out to investigate the role of D-512, a potent multifunctional neuroprotective D2/D3 receptor agonist, in protecting dopaminergic PC12 cells treated with buthionine sulfoximine (BSO), an inhibitor of key enzyme in glutathione synthesis and 6-hydroxydopamine (6-OHDA), a widely used neurotoxin. D-512 was able to restore level of glutathione against BSO/6-OHDA-mediated glutathione depletion. D-512 also showed significant neuroprotection in PC12 cells against toxicity induced by combined treatment of BSO and 6-OHDA. Furthermore, D-512 was able to restore both phospho-extracellular signal-regulated kinase and phospho-Jun N-terminal kinase levels upon treatment with 6-OHDA providing an evidence on the possible mechanism of action for neuroprotection by modulating mitogen-activated protein kinases. We have further demonstrated the neuroprotective effects of D-512 against oxidative insult produced by BSO and 6-OHDA in PC12 cells.
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影响因子：
4.3
作者：
Jomova, Klaudia;Vondrakova, Dagmar;Valko, Marian
通讯作者：
Valko, Marian
影响因子：
4.7
作者：
Alam, ZI;Jenner, A;Halliwell, B
通讯作者：
Halliwell, B
影响因子：
2.4
作者：
Hwang O
通讯作者：
Hwang O
DOI：
10.1007/978-1-60761-795-2_1
发表时间：
2010-01-01
期刊：
MAP KINASE SIGNALING PROTOCOLS, SECOND EDITION
影响因子：
--
作者：
Keshet, Yonat;Seger, Rony
通讯作者：
Seger, Rony
谷胱甘肽消耗对 PC12 细胞中溴氰菊酯 Nrf2/Are 激活的影响
DOI：
10.2478/10004-1254-64-2013-2251
发表时间：
2013-03-01
影响因子：
2.1
作者：
Li, Huangyuan;Wu, Siying;Shi, Nian
通讯作者：
Shi, Nian