title: The role of HO-1 in protection against lead-induced neurotoxicity.
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.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Fang
authors.initials: F
authors.lastname: Ye
authors.affiliation: 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.
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. Electronic address: xiongwenwu@hotmail.com.
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D000066829:Neuroprotection / Q000187:drug effects*; D009942:Organometallic Compounds / Q000633:toxicity*; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D009942:Organometallic Compounds; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; C008261:lead acetate
keywords: Cell death; Cytoprotective effects; HO-1; Neurotoxicity; PbAc