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细胞外酸中毒、半胱氨酸和谷胱甘肽增强小脑颗粒神经元培养物中铜离子的毒性作用。

Extracellular Acidosis, Cysteine, and Glutathione Enhance the Toxic Effect of Copper Ions in Cultures of Cerebellar Granule Neurons.

机构信息

Research Center of Neurology, Moscow, Russia.

Lomonosov Moscow State University, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2024 Sep;177(5):588-591. doi: 10.1007/s10517-024-06229-2. Epub 2024 Sep 28.

DOI:10.1007/s10517-024-06229-2
PMID:39342006
Abstract

We studied the effect of extracellular acidosis, cysteine, glutathione, and iron ions (Fe) on the neurocytotoxic effect of copper ions (Cu) in vitro. At acidic pH of the culture medium (pH 6.8), the toxic effect of copper on cultured neurons significantly increased in comparison with that at neutral pH 7.3. In the presence of 25 μM Cu in the culture medium at pH 7.3 and 6.8, the neuronal survival was 89±2 and 63±4%, respectively. In the presence of glutathione or cysteine (1 μM) in the culture medium, even 0.5 μM Cu caused 100% death of cultured neurons, while the presence of Fe (10-50 μM) had no effect on the toxicity of Cu. In general, acidosis or the presence of glutathione or cysteine increases the cytotoxicity of copper ions.

摘要

我们研究了细胞外酸中毒、半胱氨酸、谷胱甘肽和铁离子(Fe)对铜离子(Cu)在体外的神经细胞毒性的影响。在培养基的酸性 pH 值(pH 6.8)下,与中性 pH 值 7.3 相比,铜对培养神经元的毒性作用明显增加。在 pH 值为 7.3 和 6.8 的培养基中存在 25 μM Cu 的情况下,神经元的存活率分别为 89±2%和 63±4%。在培养基中存在谷胱甘肽或半胱氨酸(1 μM)的情况下,即使存在 0.5 μM Cu 也会导致培养神经元 100%死亡,而铁(10-50 μM)的存在对 Cu 的毒性没有影响。总的来说,酸中毒或谷胱甘肽或半胱氨酸的存在增加了铜离子的细胞毒性。

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本文引用的文献

1
Copper neurotoxicity: Induction of cognitive dysfunction: A review.铜神经毒性:认知功能障碍的诱导:综述。
Medicine (Baltimore). 2023 Dec 1;102(48):e36375. doi: 10.1097/MD.0000000000036375.
2
Copper homeostasis and cuproptosis in health and disease.铜稳态和铜死亡在健康和疾病中的作用。
Signal Transduct Target Ther. 2022 Nov 23;7(1):378. doi: 10.1038/s41392-022-01229-y.
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Toxic Effect of Zinc Ions Is Accompanied by Acidification of the Cytoplasm in Cultured Rat Cerebellar Granule Neurons.培养的大鼠小脑颗粒神经元中锌离子的毒性作用伴随着细胞质酸化。
Bull Exp Biol Med. 2022 Aug;173(4):539-543. doi: 10.1007/s10517-022-05578-0. Epub 2022 Sep 5.
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Cerebral Iron Deposition in Neurodegeneration.脑铁沉积与神经变性疾病。
Biomolecules. 2022 May 17;12(5):714. doi: 10.3390/biom12050714.
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Study on different pathogenic factors in different disease stages of patients with Wilson disease.对肝豆状核变性患者不同疾病阶段不同致病因素的研究。
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Copper Dyshomeostasis in Neurodegenerative Diseases-Therapeutic Implications.铜代谢失衡与神经退行性疾病——治疗意义。
Int J Mol Sci. 2020 Dec 4;21(23):9259. doi: 10.3390/ijms21239259.
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Role of zinc and copper ions in the pathogenetic mechanisms of traumatic brain injury and Alzheimer's disease.锌离子和铜离子在创伤性脑损伤和阿尔茨海默病发病机制中的作用。
Rev Neurosci. 2020 Apr 28;31(3):233-243. doi: 10.1515/revneuro-2019-0052.
8
N-Acetyl-L-cysteine in the Presence of Cu Induces Oxidative Stress and Death of Granule Neurons in Dissociated Cultures of Rat Cerebellum.在铜存在的情况下,N-乙酰-L-半胱氨酸诱导大鼠小脑解离培养物中颗粒神经元的氧化应激和死亡。
Biochemistry (Mosc). 2017 Oct;82(10):1176-1182. doi: 10.1134/S0006297917100108.
9
Role of zinc and copper ions in the pathogenetic mechanisms of Alzheimer's and Parkinson's diseases.锌离子和铜离子在阿尔茨海默病和帕金森病发病机制中的作用。
Biochemistry (Mosc). 2014 May;79(5):391-6. doi: 10.1134/S0006297914050022.
10
Metabolism and functions of copper in brain.脑内铜的代谢和功能。
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