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Zinc-pretreatment triggers glutathione and Nrf2-mediated protection against inorganic mercury-induced cytotoxicity and intrinsic apoptosis in PC12 cells

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Title: Zinc-pretreatment triggers glutathione and Nrf2-mediated protection against inorganic mercury-induced cytotoxicity and intrinsic apoptosis in PC12 cells
Authors: Hossain, Kaniz Fatima Binte Browse this author
Hosokawa, Toshiyuki Browse this author →KAKEN DB
Saito, Takeshi Browse this author →KAKEN DB
Kurasaki, Masaaki Browse this author →KAKEN DB
Keywords: Hemeoxygenese1
Cytochrome c
ERK1
Antioxidant
Oxidative stress
Issue Date: 1-Jan-2021
Publisher: Elsevier
Journal Title: Ecotoxicology and environmental safety
Volume: 207
Start Page: 111320
Publisher DOI: 10.1016/j.ecoenv.2020.111320
Abstract: 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 inves-tigate the effect of Zn on inorganic Hg-induced cytotoxicity in the PC12 cells. The cells were treated with HgCl2 (5 mu M) for 48 h with/without 1 h prior ZnCl2-treatment (100 mu M) 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.
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article
URI: http://hdl.handle.net/2115/80230
Appears in Collections:環境科学院・地球環境科学研究院 (Graduate School of Environmental Science / Faculty of Environmental Earth Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 藏崎 正明

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