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Mahmoudi-Nejad S, Abdirad I, Bagheri M. Zinc Mitigates MDMA-Prompted Apoptosis by Alteration of Cross Talk Among Bcl-2, Bax and P53 Genes Expression in Mouse Sertoli and Leydig Cell Lines. rbmb.net 2024; 13 (3) :420-427
URL: http://rbmb.net/article-1-1514-en.html
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.
Abstract:   (340 Views)
Background: 3,4-methylenedioxymethamphetamine (MDMA) affects the male reproductive system. We investigated the mRNA levels of bax, bcl-2, and p53 genes in MDMA-induced apoptosis in mouse Sertoli (TM4) and Leydig (TM3) cells before and after taking Zinc.

Methods: The TM3 and TM4 cells were cultured in four groups: I (untreated medium), II (medium with 5 mM MDMA), III (medium with 8 µM Zinc), and IV (medium with 8 µM Zinc prior to 5 mM MDMA administration). After 48 hours, total RNA was extracted from the samples, and cDNA was synthesized. The relative gene expression level was evaluated using the SYBR Green PCR kit.

Results: In the MDMA group, the relative amounts of bax and p53 gene expressions increased; conversely, the relative amount of bcl-2 gene expression decreased in TM3 and TM4 cell lines. In the MDMA+Zinc group, there were no statistically significant differences between this group and the control group regarding the mRNA levels of bax and p53 genes in the TM3 cell line, as well as the mRNA levels of bax and bcl-2 genes in the TM4 cell line. Statistically significant differences were observed between the MDMA+Zinc and MDMA groups regarding the relative expressions of bax and p53 genes in the TM3 cell line and bcl-2 and p53 genes in the TM4 cell line.

Conclusions: Zinc mitigates MDMA- induced apoptosis by altering the crosstalk among bcl-2, bax, and p53 gene expressions in the tested cell lines.
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Type of Article: Original Article | Subject: Molecular Biology
Received: 2024/11/16 | Accepted: 2025/02/16 | Published: 2025/04/12

References
1. Hossein-Zadeh N, Bagheri M, Abdi Rad I, Lozeie M, Nasir-Zadeh M. Zinc Protects against MDMA-Induced Apoptosis of Sertoli Cells in Mouse via Attenuation of Caspase-3. Int J Fertil Steril. 2020;14(3):223-227.
2. Capela JP, Carvalho FD. A review on the mitochondrial toxicity of "ecstasy" (3,4-methylenedioxymethamphetamine, MDMA). Curr Res Toxicol. 2022; 3:100075. [DOI:10.1016/j.crtox.2022.100075] [PMID] []
3. Marina P, Annamaria L, Barbara D, Loredana R, Piero A, Francesco A. Fine structure of leydig and sertoli cells in the testis of immature and mature spotted ray Torpedo marmorata. Mol Reprod Dev. 2002;63(2):192-201. [DOI:10.1002/mrd.10162] [PMID]
4. Song BJ, Moon KH, Upreti VV, Eddington ND, Lee IJ. Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage. Curr Pharm Biotechnol. 2010;11(5):434-43. [DOI:10.2174/138920110791591436] [PMID] []
5. Barenys M, Macia N, Camps L, de Lapuente J, Gomez-Catalan J, Gonzalez-Linares J, et al. Chronic exposure to MDMA (ecstasy) increases DNA damage in sperm and alters testes histopathology in male rats. Toxicol Lett. 2009;191(1):40-6. [DOI:10.1016/j.toxlet.2009.08.002] [PMID]
6. Tsai SC, Chiao YC, Lu CC, Doong ML, Chen YH, Shih HC, Liaw C, et al. Inhibition by amphetamine of testosterone secretion through a mechanism involving an increase of cyclic AMP production in rat testes. Br J Pharmacol. 1996;118(4):984-8. [DOI:10.1111/j.1476-5381.1996.tb15496.x] [PMID] []
7. Pourhassanali N, Roshan-Milani S, Kheradmand F, Motazakker M, Bagheri M, Saboory E. Zinc attenuates ethanol-induced Sertoli cell toxicity and apoptosis through caspase-3 mediated pathways. Reprod Toxicol. 2016; 61:97-103. [DOI:10.1016/j.reprotox.2016.03.041] [PMID]
8. Marreiro DD, Cruz KJ, Morais JB, Beserra JB, Severo JS, de Oliveira AR. Zinc and Oxidative Stress: Current Mechanisms. Antioxidants (Basel). 2017;6(2):24. [DOI:10.3390/antiox6020024] [PMID] []
9. Lozeie M, Bagheri M, Rad IA, Hossein-Zadeh N, Nasir-Zadeh M. Zinc attenuates ecstasy-induced apoptosis through downregulation of caspase-3 in cultured TM3 cells: An experimental study. Int J Reprod Biomed. 2020;18(9):777-784. [DOI:10.18502/ijrm.v13i9.7672] [PMID] []
10. Arifin WN, Zahiruddin WM. Sample Size Calculation in Animal Studies Using Resource Equation Approach. Malays J Med Sci. 2017;24(5):101-105. [DOI:10.21315/mjms2017.24.5.11] [PMID] []
11. Ghatei N, Nabavi AS, Toosi MHB, Azimian H, Homayoun M, Targhi RG, Haghir H. Evaluation of bax, bcl-2, p21 and p53 genes expression variations on cerebellum of BALB/c mice before and after birth under mobile phone radiation exposure. Iran J Basic Med Sci. 2017; 20(9):1037-1043.
12. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8. [DOI:10.1006/meth.2001.1262] [PMID]
13. Del Rio MJ, Velez-Pardo C. Monoamine neurotoxins-induced apoptosis in lymphocytes by a common oxidative stress mechanism: involvement of hydrogen peroxide (H(2)O(2)), caspase-3, and nuclear factor kappa-B (NF-kappaB), p53, c-Jun transcription factors. Biochem Pharmacol. 2002; 63(4): 677-88. [DOI:10.1016/S0006-2952(01)00907-8] [PMID]
14. Cui Q, Yu JH, Wu JN, Tashiro S, Onodera S, Minami M, et al. P53-mediated cell cycle arrest and apoptosis through a caspase-3- independent, but caspase-9-dependent pathway in oridonin-treated MCF-7 human breast cancer cells. Acta Pharmacol Sin. 2007; 28(7): 1057-66. [DOI:10.1111/j.1745-7254.2007.00588.x] [PMID]
15. Montiel-Duarte C, Varela-Rey M, Osés-Prieto JA, López-Zabalza MJ, Beitia G, Cenarruzabeitia E, et al. 3,4-Methylenedioxymethamphetamine ("Ecstasy") induces apoptosis of cultured rat liver cells. Biochim Biophys Acta. 2002;1588(1): 26-32. [DOI:10.1016/S0925-4439(02)00112-6] [PMID]
16. Wang Q, Zhang L, Yuan X, Ou Y, Zhu X, Cheng Z, et al. The Relationship between the Bcl-2/Bax Proteins and the Mitochondria-Mediated Apoptosis Pathway in the Differentiation of Adipose-Derived Stromal Cells into Neurons. PLoS One. 2016; 11(10):e0163327. [DOI:10.1371/journal.pone.0163327] [PMID] []
17. Simantov R, Tauber M. The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic cells. FASEB J. 1997;11(2):141-6. [DOI:10.1096/fasebj.11.2.9039956] [PMID]
18. El-Merahbi R, Löffler M, Mayer A, Sumara G. The roles of peripheral serotonin in metabolic homeostasis. FEBS Lett. 2015;589(15):1728-34. [DOI:10.1016/j.febslet.2015.05.054] [PMID]
19. Tofigh P, Mirghazanfari SM, Hami Z, Nassireslami E, Ebrahimi M. The Investigation of Quercus Infectoria Gall Aqueous Extract Effect on the Cell Proliferation, Apoptosis and Expression of CCND1, TP53, BCL2 and BAX Genes in Cell Line of Lung, Gastric and Esophageal Cancers. Rep Biochem Mol Biol. 2024;12(4):596-608. [DOI:10.61186/rbmb.12.4.596] [PMID] []
20. Mahmoudi-Nejad S, Ahmadi S, Hassan-Nejhad M, Azimi M, Dadvand H, Bagheri M. Zinc Supplementation Reduces ROS Production and Prevents MDMA-Induced Apoptosis in TM3 Leydig Cells via the Inhibition of Pro-Apoptotic Proteins. Biol Trace Elem Res. 2024. doi: 10.1007/s12011-024-04302-5. [DOI:10.1007/s12011-024-04302-5] [PMID]
21. Taghizadeh G, Pourahmad J, Mehdizadeh H, Foroumadi A, Torkaman-Boutorabi A, Hassani S, Naserzadeh P, Shariatmadari R, Gholami M, Rouini MR, Sharifzadeh M. Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment. Free Radic Biol Med. 2016; 99:11-19. [DOI:10.1016/j.freeradbiomed.2016.07.018] [PMID]
22. Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Reed JC. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 1994;9(6):1799-805.
23. Selvakumaran M, Lin HK, Miyashita T, Wang HG, Krajewski S, Reed JC, Hoffman B, Liebermann D. Immediate early up-regulation of bax expression by p53 but not TGF beta 1: a paradigm for distinct apoptotic pathways. Oncogene. 1994; 9(6):1791-8.
24. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993;74(4):609-19. [DOI:10.1016/0092-8674(93)90509-O] [PMID]
25. Zolfaghari B, Ghanbari M, Musavi H, Bavandpour Baghshahi P, Taghikhani M, Pourfallah F. Investigation of Zinc Supplement Impact on the Serum Biochemical Parameters in Pulmonary Tuberculosis: A Double Blinded Placebo Control Trial. Rep Biochem Mol Biol. 2021;10(2):173-182. [DOI:10.52547/rbmb.10.2.173] [PMID] []
26. Maret W. Zinc biochemistry: from a single zinc enzyme to a key element of life. Adv Nutr. 2013;4(1):82-91. [DOI:10.3945/an.112.003038] [PMID] []
27. Ajibare AJ, Odetayo AF, Akintoye OO, Olayaki LA. Zinc ameliorates acrylamide-induced oxidative stress and apoptosis in testicular cells via Nrf2/HO-1/NfkB and Bax/Bcl2 signaling pathway. Redox Rep. 2024;29(1):2341537. [DOI:10.1080/13510002.2024.2341537] [PMID] []
28. Fallah A, Mohammad-Hasani A, Colagar AH. Zinc is an Essential Element for Male Fertility: A Review of Zn Roles in Men's Health, Germination, Sperm Quality, and Fertilization. J Reprod Infertil. 2018;19(2):69-81.
29. Yamaguchi S, Miura C, Kikuchi K, Celino FT, Agusa T, Tanabe S, et al. Zinc is an essential trace element for spermatogenesis. Proc Natl Acad Sci U S A. 2009; 106(26): 10859-64. [DOI:10.1073/pnas.0900602106] [PMID] []
30. Xu G, Shi Y. Apoptosis signaling pathways and lymphocyte homeostasis. Cell Res. 2007;17(9):759-71. [DOI:10.1038/cr.2007.52] [PMID]

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