作者
孔 伟,任小桐,柳赟昊
文章摘要
目的:探究自噬在氯化镉(CdCl2)诱导小鼠睾丸间质细胞凋亡中的作用机制。方法:不同浓度CdCl2(0、5和10μmol/L)染毒细胞24h,Western blot检测细胞内凋亡蛋白cleaved Caspase-3和cleaved Caspase-9以及自噬相关蛋LC3、p62蛋白表达水平。分别用自噬抑制剂3-甲基腺嘌呤(3-Methyladenine,3MA)(60µmol/L)和自噬激动剂雷帕霉素(Rapamycin,RAP)(50nmol/L)与CdCl2(10μmol/L)染毒TM3细胞24h,Western blot检测细胞内LC3、p62、cleaved Caspase-3和cleaved Caspase-9蛋白表达水平的变化。结果:与对照组细胞相比,随着CdCl2浓度增加,cleaved Caspase-9, cleaved Caspase-3、LC3-II和p62蛋白表达水平显著升高(P < 0.05)。与CdCl2组相比,CdCl2与3-MA共处理组细胞中LC3-II、p62、cleaved Caspase-9和cleaved Caspase-3蛋白的表达显著下调(P<0.001),CdCl2与RAP共处理组细胞中四种蛋白的表达水平也均显著降低(P<0.001)。结论:氯化镉可能通过阻滞自噬流,促使自噬体异常聚集,引起睾丸间质细胞凋亡发生。
文章关键词
镉;睾丸间质细胞;自噬体;凋亡
参考文献
[1] Zhou Z, Zheng D, Wu H, et al. Epidemiology of infertility in China: a population-based study[J]. BJOG, 2018, 125(4):432-441.
[2] Agarwal A, Mulgund A, Hamada A, et al. A unique view on male infertility around the globe[J]. Reprod Biol Endocrinol, 2015, 13:37.
[3] Sharma A, Mollier J, Brocklesby R, et al. Endocrine-disrupting chemicals and male reproductive health[J]. Reprod Med Biol, 2020, 19(3):243-253.
[4] Rafati RM, Rafati RM, Kazemi S, et al. Cadmium toxicity and treatment: An update[J]. Caspian J Intern Med, 2017, 8(3):135-145.
[5] Zhu Q, Li X, Ge RS. Toxicological Effects of Cadmium on Mammalian Testis[J]. Front Genet, 2020, 11:527.
[6] Gong YG,Wang YQ,Gu M,et al.Deprival of testicular innervation induces apoptosis of leydig cells via caspase-8-dependent signaling: a novel survival pathway revealed[J]. Biochem Biophys Res Commun, 2009, 382(1):165-170
[7] Yi L, Shang XJ, Lv L, et al. Cadmium-induced apoptosis of Leydig cells is mediated by excessive mitochondrial fission and inhibition of mitophagy[J]. Cell Death Dis. 2022, 13(11):928.
[8] De Franciscis P, Ianniello R, Labriola D, et al. Environmental pollution due to cadmium: measure of semen quality as a marker of exposure and correlation with reproductive potential[J]. Clin Exp Obstet Gynecol, 2015, 42(6):767-770.
[9] Wijesekara GU, Fernando DM, Wijerathna S, et al. Environmental and occupational exposures as a cause of male infertility[J]. Ceylon Med J, 2015, 60(2):52-56.
[10] Neweshy MS, Maddawy ZK, Sayed YS. Therapeutic effects of date palm (Phoenix dactylifera L.) pollen extract on cadmium-induced testicular toxicity[J]. Andrologia, 2013, 45(6):369-378.
[11] Chen CY, Mruk D. The blood-testis barrier and its implications for male contraception[J]. Pharmacol Rev, 2012, 64(1):16-64.
[12] Yoshii SR, Mizushima N. Monitoring and measuring autophagy[J]. Int J Mol Sci, 2017, 18(9):1865.
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