t-BHQ Provides Protection against Lead Neurotoxicity via Nrf2/HO-1 Pathway

Oxidative Medicine and Cellular Longevity
Fang YeJun Chen

Abstract

The neurotoxicity of lead has been well established, and oxidative stress is strongly associated with lead-induced neurotoxicity. Nrf2 is important for protection against oxidative stress in many disease models. We applied t-BHQ, which is an Nrf2 activator, to investigate the possible role of Nrf2 in the protection against lead neurotoxicity. t-BHQ significantly attenuated the oxidative stress in developmental rats by decreasing MDA level, as well as by increasing SOD activity and GSH content, in the hippocampus and frontal cortex. Furthermore, neuronal apoptosis was detected by Nissl staining, and Bax expression was inhibited in the t-BHQ-treated group. Results showed that t-BHQ suppressed ROS production and caspase 3/7 activity but increased intracellular GSH content, in SH-SY5Y cells under lead exposure. Moreover, in vivo and in vitro, t-BHQ enhanced the nuclear translocation of Nrf2 and binding to ARE areas but did not induce Nrf2 transcription. These phenomena were confirmed using RT-PCR, EMSA, Western blot, and immunofluorescence analyses. Subsequent upregulation of the expression of HO-1, NQO1, and GCLC was observed. However, knockdown of Nrf2 or HO-1 adversely affected the protective effects of t-BHQ against lead toxici...Continue Reading

References

Nov 1, 1995·Biological Trace Element Research·S J Yiin, T H Lin
Jan 19, 2000·Clinical Biochemistry·J M MatésI Núñez de Castro
Oct 9, 2002·Current Drug Metabolism·Thomas H Rushmore, A-N Tony Kong
Dec 13, 2002·Brain : a Journal of Neurology·Theodore I Lidsky, Jay S Schneider
Jan 30, 2004·Annual Review of Medicine·Herbert Needleman
Mar 3, 2004·Human & Experimental Toxicology·Pradeep K ShuklaRikhab C Srimal
Apr 19, 2005·Archives of Pharmacal Research·Changjiang XuAh-Ng Tony Kong
Jul 7, 2005·The Journal of Experimental Medicine·Tirumalai RangasamyShyam Biswal
Nov 4, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andy Y ShihTimothy H Murphy
Oct 2, 2007·Toxicology and Applied Pharmacology·L D WhiteMd Riyaz Basha
Jul 12, 2008·Molecular Carcinogenesis·Wenge Li, Ah-Ng Kong
Aug 1, 2008·Archives of Toxicology·Sandra V VerstraetenPatricia I Oteiza
Jan 24, 2009·Trends in Molecular Medicine·Miguel P Soares, Fritz H Bach
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Pei-Chun ChenJeffrey A Johnson
Jan 9, 2010·Annual Review of Pharmacology and Toxicology·Raffaella GozzelinoMiguel P Soares
Feb 19, 2010·Biomedical and Environmental Sciences : BES·Yu-Mei ZhangZong-Ping Liu
Jun 2, 2010·Journal of Physiology and Biochemistry·Enas A HamedNashwa A Abd El-Mottaleb
Jun 24, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Richard Changxun LiDavid Gozal
Nov 3, 2012·Interdisciplinary Toxicology·Gagan FloraArchana Tiwari
Jan 1, 2013·Free Radical Biology & Medicine·Suryakant K Niture, Anil K Jaiswal
Nov 10, 2013·Free Radical Biology & Medicine·Hye-Kyung Na, Young-Joon Surh
Mar 20, 2014·Free Radical Biology & Medicine·Jianguo XuXinyu Lu

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Citations

Jul 12, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bin ZhangXiaobo Sun
Aug 4, 2018·International Journal of Molecular Sciences·Mariapaola NittiAnna Lisa Furfaro
Aug 16, 2019·International Journal of Environmental Research and Public Health·Al Omar S YousefRami B Kassab
Dec 5, 2017·Experimental and Therapeutic Medicine·Shumei CaoQiaohong Hei
Sep 14, 2018·Frontiers in Molecular Neuroscience·Md JakariaDong-Kug Choi
Jan 6, 2021·Antioxidants·Melania Guerrero-HueJuan Antonio Moreno
Mar 14, 2018·Neurochemistry International·Juan ZhangQuanguang Zhang

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Methods Mentioned

BETA
MDA
ubiquitination
protein assay
Flow cytometry
transfection
electrophoresis
Assay
Nuclear Translocation

Software Mentioned

ImageJ
Oligonucleotide Microarray Analysis

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