首页> 外文学位 >Glutathione depletion in neurodegenerative disorders: Cell death mechanisms and neuroprotection, exacerbation of manganese neurotoxicity, and the role in glutathione regeneration pathway.

【24h】

Glutathione depletion in neurodegenerative disorders: Cell death mechanisms and neuroprotection, exacerbation of manganese neurotoxicity, and the role in glutathione regeneration pathway.

机译：谷胱甘肽在神经退行性疾病中的耗竭：细胞死亡机制和神经保护作用，锰神经毒性的恶化以及在谷胱甘肽再生途径中的作用。

获取原文

获取原文并翻译 | 示例

页面导航

摘要
著录项
相似文献
相关主题

摘要

Glutathione (GSH) (gamma-glutamyl cysteinyl glycine) is an antioxidant biosynthesisized in cells and is vital in maintaining the cellular redox environment. Depletion in GSH levels is reported in neurodegenerative disorders including Parkinson's disease. GSH depletion could lead to cellular oxidative stress and ultimately cell death. Regeneration of reduced GSH is an important aspect of GSH metabolism which needs reducing equivalent of NADPH and could control the availability of GSH to neutralize reactive oxygen species. GSH also helps in the cellular defense against xenobiotics such as toxic metals and thus depletion of GSH may enhance neurotoxicity of manganese. Molecular mechanisms of cell death induced by GSH depletion are not fully understood. Moreover, despite numerous research reports on GSH, the potential use of GSH in the pharmacotherapy of neurodegenerative disorders has not yet been achieved. Thus, we attempted to decipher the process of GSH depletion-induced cell death. Our results show that mitochondrial GSH plays a regulatory role in mitochondria-mediated apoptosis process induced by GSH depletion. We also confirmed the neuroprotective potential of astrocytes in a GSH depletion paradigm. Moreover, our research suggests that GSH depletion could be one of the mechanisms underlying Mn neurotoxicity. We also studied developmental changes and sexual dimorphism of activities of the enzymes of GSH regeneration pathway. Our research clearly contributes to an improved understanding of the role of GSH depletion in etiology of neurodegenerative disorders and could be helpful in developing potential pharmacotherapy for such diseases.

机译：谷胱甘肽（GSH）（γ-谷氨酰胺基半胱氨酸甘氨酸）是一种在细胞中生物合成的抗氧化剂，对维持细胞氧化还原环境至关重要。据报道，包括帕金森氏症在内的神经退行性疾病中GSH含量减少。 GSH耗竭可能导致细胞氧化应激并最终导致细胞死亡。还原型GSH的再生是GSH代谢的重要方面，它需要减少NADPH的当量，并可以控制GSH的可用性以中和活性氧。谷胱甘肽还有助于抵抗诸如毒素之类的异种生物的细胞防御，因此，谷胱甘肽的耗尽可能会增强锰的神经毒性。 GSH耗竭诱导的细胞死亡的分子机制尚未完全了解。此外，尽管有大量关于GSH的研究报告，但尚未实现GSH在神经退行性疾病的药物治疗中的潜在用途。因此，我们试图破译GSH耗竭诱导的细胞死亡的过程。我们的结果表明，线粒体GSH在由GSH耗竭诱导的线粒体介导的细胞凋亡过程中起调节作用。我们还证实了GSH耗竭范式中星形胶质细胞的神经保护潜力。此外，我们的研究表明GSH耗竭可能是Mn神经毒性的潜在机制之一。我们还研究了GSH再生途径酶活性的发育变化和性二态性。我们的研究显然有助于增进对GSH耗竭在神经退行性疾病病因中的作用的了解，并可能有助于开发此类疾病的潜在药物疗法。

著录项

作者
Dukhande, Vikas Vasudeo.;
展开▼
作者单位

Idaho State University.;

展开▼
授予单位 Idaho State University.;
学科 Health Sciences Pharmacology.;Biology Neuroscience.
学位 Ph.D.
年度 2009
页码 131 p.
总页数 131
原文格式 PDF
正文语种 eng
中图分类宗教史、宗教地理;
关键词

相似文献

外文文献
中文文献
专利

1. Manganese-induced neurotoxicity is differentially enhanced by glutathione depletion in astrocytoma and neuroblastoma cells. [J] . Dukhande VV, Malthankar-Phatak GH, Hugus JJ, Neurochemical research . 2006,第11期

机译：星形胶质细胞瘤和神经母细胞瘤细胞中谷胱甘肽耗竭可不同程度地增强锰引起的神经毒性。
2. Neuroprotection against neuroblastoma cell death induced by depletion of mitochondrial glutathione [J] . Dukhande V.V., Kawikova I., Bothwell A.L.M., Apoptosis: An international journal on programmed cell death . 2013,第6期

机译：线粒体谷胱甘肽耗竭诱导的神经母细胞瘤细胞死亡的神经保护
3. Lipopolysaccharide prevents cell death caused by glutathione depletion: possible mechanisms of protection. [J] . Kramer B, Yabut J, Cheong J, Neuroscience: An International Journal under the Editorial Direction of IBRO . 2002,第2期

机译：脂多糖可防止由谷胱甘肽耗竭引起的细胞死亡：可能的保护机制。
4. Depletion of Intracellular Glutathione of Setaria cervi by Buthionine sulfoximine, Carmustine and their analogues [C] . Sapna GUPTA, Ramapati TRIPATHI, Arvind K SRIVASTAVA, World Multiconference on Systemics, Cybernetics and Informatics(SCI 2002) v.17: Industrial Systems and Engineering III; 20020714-20020718; Orlando,FL; US . 2002

机译：丁硫氨酸亚胺，卡莫斯汀及其类似物消耗子宫颈内谷胱甘肽的能力
5. Mechanisms of methylmercury-induced toxicity in primary embryonic CNS cells: The role of cell cycle regulatory genes and glutathione. [D] . Ou, Ying-Chung. 1997

机译：甲基汞诱导的原始胚胎CNS细胞毒性的机制：细胞周期调控基因和谷胱甘肽的作用。
6. Neuroprotection against neuroblastoma cell death induced by depletion of mitochondrial glutathione [O] . Vikas V. Dukhande, Ivana Kawikova, Alfred L.M. Bothwell, -1

机译：线粒体谷胱甘肽耗竭诱导的神经母细胞瘤细胞死亡的神经保护
7. Metabotropic glutamate receptor 3 neuroprotection A. Berent-Spillson and J. W. Russell Received June 12, 2006; revised manuscript received October 3, 2006; accepted October 5, 2006. Address correspondence and reprint requests to James W. Russell, Department of Neurology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201-1595, USA. E-mail: jruss@umich.edu Abbreviations used : APDC , 2 R ,4 R -4-aminopyrrolidine-2,4-dicarboxylate (specific metabotropic glutamate receptor 3 agonist) ; BSO , buthionine sulfoximine (GSH synthesis inhibitor) ; caspase , cysteine-requiring aspartate protease ; CysGly , cysteinylglycine (GSH degradation product) ; DAPI , 4′-6-diamidino-2-phenylindole ; DCF , dichlorodihydrofluorescein ; DCFDA , 5-(and 6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, acetyl ester ; DHE , dihydroethidium ; DRG , dorsal root ganglion ; FCCP , carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (electron transport uncoupler) ; GCP II/III , glutamate carboxypeptidase II/III ; GSH , glutathione ; GSH-EE , glutathione ethyl ester ; GST , glutathione-s-transferase ; H 2 O 2 , hydrogen peroxide ; HBSS , Hank’s balanced salt solution ; JC-1 , 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide ; MCB , monochlorobimane ; mGluR , metabotropic glutamate receptor ; NAAG , N -acetyl-aspartyl-glutamate ; PBS , phosphate-buffered saline ; PCD , programmed cell death ; Rh123 , rhodamine123 ; ROS , reactive oxygen species ; δψ μ , inner mitochondrial membrane potential . Metabotropic glutamate receptor 3 protects neurons from glucose-induced oxidative injury by increasing intracellular glutathione concentration [O] . Berent-Spillson Alison, Russell James W. 2007

机译：代谢型谷氨酸受体3神经保护a. Berent-spillson和J. W. Russell于2006年6月12日收到;修订稿于2006年10月3日收到; 2006年10月5日接受。美国马里兰州巴尔的摩市南格林街22号，马里兰大学医学院神经病学系James W. Russell的地址通信和重印申请。电子邮件：jruss@umich.edu使用的缩写：apDC，2R，4R-4-氨基吡咯烷-2,4-二羧酸酯（特异性代谢型谷氨酸受体3激动剂）; BsO，丁硫氨酸亚砜亚胺（GsH合成抑制剂）;半胱天冬酶，半胱氨酸需要的天冬氨酸蛋白酶; CysGly，半胱氨酰甘氨酸（GsH降解产物）; DapI，4'-6-二脒基-2-苯基吲哚; DCF，二氯二氢荧光素; DCFDa，5-（和6） - 氯甲基-2'，7'-二氯二氢荧光素二乙酸酯，乙酰酯; DHE，二氢乙锭; DRG，背根神经节; FCCp，羰基氰化物4-（三氟甲氧基）苯腙（电子传输解偶联剂）; GCp II / III，谷氨酸羧肽酶II / III;谷胱甘肽;谷胱甘肽; GsH-EE，谷胱甘肽乙酯; GsT，谷胱甘肽-s-转移酶; H 2 O 2，过氧化氢; HBss，Hank的平衡盐溶液; JC-1,5,5'，6,6'-四氯-1,1'，3,3'-四乙基苯并咪唑基酞菁碘化物; mCB，monochlorobimane; mGluR，代谢型谷氨酸受体; NaaG，N-乙酰基 - 天冬氨酰谷氨酸; pBs，磷酸盐缓冲盐水; pCD，程序性细胞死亡; Rh123，罗丹明123;活性氧，活性氧; δψμ，线粒体内膜电位。代谢型谷氨酸受体3通过增加细胞内谷胱甘肽浓度来保护神经元免受葡萄糖诱导的氧化损伤

Glutathione depletion in neurodegenerative disorders: Cell death mechanisms and neuroprotection, exacerbation of manganese neurotoxicity, and the role in glutathione regeneration pathway.

摘要

著录项

相似文献

相关主题

期刊订阅