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补充锌通过抑制促凋亡蛋白减少ROS生成并预防MDMA诱导的TM3 Leydig细胞凋亡。

Zinc Supplementation Reduces ROS Production and Prevents MDMA-Induced Apoptosis in TM3 Leydig Cells via the Inhibition of Pro-Apoptotic Proteins.

作者信息

Mahmoudi-Nejad Salar, Ahmadi Sina, Hassan-Nejhad Mahssa, Azimi Mahdieh, Dadvand Hanieh, Bagheri Morteza

机构信息

Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.

Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.

出版信息

Biol Trace Elem Res. 2025 Apr;203(4):2132-2138. doi: 10.1007/s12011-024-04302-5. Epub 2024 Jul 15.

DOI:10.1007/s12011-024-04302-5
PMID:39004669
Abstract

MDMA can cause serious adverse effects on vital organs such as the heart, brain, and liver. Additionally, MDMA consumption can also potentially cause various endocrine system dysfunctions. The previous study has shown that pre-treatment of zinc can reduce the cytotoxicity of MDMA on the Leydig cell line (TM3). In this study, we investigated the mechanisms involved in the treatment with MDMA on the apoptosis of TM3 cells and the effects of zinc pre-treatment on reducing the apoptotic effects of MDMA. TM3 cells were incubated with MDMA (5 mM), zinc (8 µM), and zinc (8 µM) prior to MDMA (5 mM) for 48 h. The cells were pre-treated with zinc for 24 h prior to the administration of MDMA, and the total culture time was 48h. The effect of different treatment groups in causing oxidative stress and apoptosis in TM3 cells was measured by DCF, TUNNEL, and western blot tests, respectively. Our results revealed that the number of DCF and tunnel-positive cells increases as a result of MDMA treatment. In addition, the treatment with MDMA increased the expression of pro-apoptotic proteins caspase 3, Bax, and p53. Conversely, the expression of anti-apoptotic protein Bcl-2 decreased. Zinc pre-treatment significantly decreased the expression of pro-apoptotic proteins and the number of tunnels and DCF-positive cells compared to the MDMA-only group. It is concluded that MDMA has a toxic effect and causes apoptosis on TM3 cells, and also, pre-treatment with zinc mitigates the ROS production and toxic effect of MDMA and MDMA-induced apoptosis in TM3 cells.

摘要

摇头丸可对心脏、大脑和肝脏等重要器官造成严重不良反应。此外,服用摇头丸还可能导致各种内分泌系统功能障碍。先前的研究表明,锌预处理可降低摇头丸对睾丸间质细胞系(TM3)的细胞毒性。在本研究中,我们调查了摇头丸处理TM3细胞凋亡所涉及的机制以及锌预处理对减轻摇头丸凋亡作用的影响。将TM3细胞分别与摇头丸(5 mM)、锌(8 µM)以及在加入摇头丸(5 mM)之前先加入锌(8 µM)孵育48小时。在给予摇头丸之前,细胞先用锌预处理24小时,总培养时间为48小时。分别通过DCF、TUNNEL和蛋白质免疫印迹试验来测定不同处理组对TM3细胞氧化应激和凋亡的影响。我们的结果显示,摇头丸处理后DCF和TUNNEL阳性细胞数量增加。此外,摇头丸处理增加了促凋亡蛋白半胱天冬酶3、Bax和p53的表达。相反,抗凋亡蛋白Bcl-2的表达降低。与仅使用摇头丸的组相比,锌预处理显著降低了促凋亡蛋白的表达以及TUNNEL和DCF阳性细胞的数量。得出的结论是,摇头丸对TM3细胞具有毒性作用并导致其凋亡,而且,锌预处理可减轻TM3细胞中活性氧的产生、摇头丸的毒性作用以及摇头丸诱导的凋亡。

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Rep Biochem Mol Biol. 2024 Oct;13(3):420-427. doi: 10.61186/rbmb.13.3.420.
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Zinc Ameliorates High Pi and Ca-Mediated Osteogenic Differentiation of Mesenchymal Stem Cells.锌改善高磷和钙介导的间充质干细胞成骨分化。
Nutrients. 2024 Nov 23;16(23):4012. doi: 10.3390/nu16234012.

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Int J Reprod Biomed. 2020 Sep 20;18(9):777-784. doi: 10.18502/ijrm.v13i9.7672. eCollection 2020 Sep.
2
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Molecules. 2019 Jan 28;24(3):457. doi: 10.3390/molecules24030457.
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Trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine induces lipid peroxidation-associated apoptosis via the intrinsic and extrinsic apoptosis pathways in a first-trimester placental cell line.
三氯乙烯代谢物S-(1,2-二氯乙烯基)-l-半胱氨酸通过内源性和外源性凋亡途径在孕早期胎盘细胞系中诱导脂质过氧化相关的细胞凋亡。
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Free Radic Biol Med. 2017 Jan;102:67-76. doi: 10.1016/j.freeradbiomed.2016.10.494. Epub 2016 Nov 9.
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