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Neurotoxicology. 2016 Jan;52:1-11. doi: 10.1016/j.neuro.2015.10.015. Epub 2015 Nov 2.

The role of HO-1 in protection against lead-induced neurotoxicity.

Author information

1
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
2
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
3
Department of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, PR China.
4
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. Electronic address: xiongwenwu@hotmail.com.
5
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. Electronic address: chen-jun@hust.edu.cn.

Abstract

Lead is a pervasive and persistent environmental pollutant that exerts deleterious effects on all living organisms and continues to threaten public health on a global scale. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme that mediates antioxidative and cytoprotective effects to maintain cellular redox homeostasis and protect cells from oxidative stress. This study was designed to explore the role of HO-1 in protection against lead neurotoxicity and the signaling pathways involved. Lead acetate (PbAc) exposure resulted in increased HO-1 expression in primary rat hippocampal neurons and SH-SY5Y cells. PbAc-induced intracellular reactive oxygen species (ROS) also increased, and cell viability decreased in SH-SY5Y cells. We further demonstrated that HO-1 could be induced by PbAc through the P38, ERK1/2, and PI3K/AKT signaling pathways in a ROS-dependent manner and through the JNK pathway in a ROS-independent manner. Further investigation revealed that HO-1 overexpression significantly restrained cell apoptosis and ROS production induced by PbAc in SH-SY5Y cells. Moreover, HO-1 knockdown aggravated PbAc-induced cell apoptosis and ROS production. Our results indicated that HO-1 was a novel protective factor that could efficiently inhibit PbAc-induced oxidative stress and cell death in the nervous system, thereby providing the potential therapeutic strategies for the prevention and treatment of lead-related diseases.

KEYWORDS:

Cell death; Cytoprotective effects; HO-1; Neurotoxicity; PbAc

PMID:
26542248
DOI:
10.1016/j.neuro.2015.10.015
[Indexed for MEDLINE]

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