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Zinc-pretreatment triggers glutathione and Nrf2-mediated protection against inorganic mercury-induced cytotoxicity and intrinsic apoptosis in PC12 cells.
Ecotoxicology and Environmental Safety ( IF 6.2 ) Pub Date : 2020-09-15 , DOI: 10.1016/j.ecoenv.2020.111320
Kaniz Fatima Binte Hossain 1 , Toshiyuki Hosokawa 2 , Takeshi Saito 3 , Masaaki Kurasaki 4
Affiliation  

Mercury (Hg) is a hazardous metal, poses environmental problems with severe human health effects; whereas zinc (Zn) is an essential micronutrient with antioxidant properties. The purpose of this research was to investigate the effect of Zn on inorganic Hg-induced cytotoxicity in the PC12 cells. The cells were treated with HgCl2 (5 μM) for 48 h with/without 1 h prior ZnCl2-treatment (100 μM) and deliberated for further analysis. After 48 h of incubation with only Hg2+, the cell showed reduced cell viability, compromised cell membrane, DNA degradation, depleted glutathione level, ROS generation and drastically increased apoptosis. Subsequently, Hg2+-treated cells demonstrated a significant downregulation of akt, mTOR, ERK1, Nrf2, HO1, Bcl-2, Bcl-xL, and upregulation of p53, Bax, cytochrome c and cleaved caspase 3, indicating intrinsic apoptosis induction. However, cells pretreated with Zn2+ before Hg2+-exposure showed a significant improvement in cell viability, cell membrane, DNA damage, glutathione level, ROS amount and apoptotic cells, with a significant upregulation in mTOR, akt, ERK1, Nrf2, HO1, Bcl-2 and Bcl-xL, and downregulation in p53, Bax, cytochrome c and cleaved caspase 3, indicating inhibition of apoptosis. The findings suggested that Zn2+-pretreatment not only improves glutathione content but also induces activation of Nrf2-HO1 pathway, which would tend to suppress Hg-cytotoxicity.



中文翻译:

锌预处理可触发谷胱甘肽和Nrf2介导的保护作用,以抵抗PC12细胞中无机汞诱导的细胞毒性和固有凋亡。

汞(Hg)是一种有害金属,会给环境造成严重影响,并危害人类健康。而锌(Zn)是具有抗氧化特性的必需微量营养素。这项研究的目的是研究锌对PC12细胞中无机汞诱导的细胞毒性的影响。在ZnCl 2处理(100μM)之前/不进行1 h的情况下,将细胞用HgCl 2(5μM)处理48 h,并进行进一步分析。仅用Hg 2+孵育48小时后,细胞显示出降低的细胞活力,受损的细胞膜,DNA降解,谷胱甘肽水平降低,ROS生成和凋亡急剧增加。随后,汞2+经处理的细胞显示出akt,mTOR,ERK1,Nrf2,HO1,Bcl-2,Bcl-xL的显着下调,以及p53,Bax,细胞色素c和裂解的胱天蛋白酶3的上调,表明内在凋亡诱导。然而,细胞预处理用Zn 2+之前汞柱2+ -曝光显示在细胞活力,细胞膜,DNA损伤,谷胱甘肽水平,ROS量和凋亡细胞一个显著改善,在mTOR的一个显著上调,AKT,ERK1,Nrf2的, HO1,Bcl-2和Bcl-xL以及p53,Bax,细胞色素c和裂解的caspase 3中的下调,表明细胞凋亡受到抑制。研究结果表明,Zn 2+预处理不仅提高了谷胱甘肽的含量,而且还诱导了Nrf2-HO1途径的活化,这将倾向于抑制Hg细胞毒性。

更新日期:2020-09-16
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