title: Low-level lead exposure attenuates the expression of three major isoforms of neural cell adhesion molecule.
abstract: Toxic lead (Pb) exposure poses serious risks to human health, especially to children at developmental stages, even at low exposure levels. Neural cell adhesion molecule (NCAM) is considered to be a potential early target in the neurotoxicity of Pb due to its role in cell adhesion, neuronal migration, synaptic plasticity, and learning and memory. However, the effect of low-level Pb exposure on the specific expression of NCAM isoforms has not been reported. In the present study, we found that Pb could concentration-dependently (1-100 nM) inhibit the expression of three major NCAM isoforms (NCAM-180, -140, and -120) in primary cultured hippocampal neurons. Furthermore, it was verified that levels of all three major isoforms of NCAM were reduced by Pb exposure in human embryonic kidney (HEK)-293 cells transiently transfected with NCAM-120, -140, or -180 isoform cDNA constructs. In addition, low-level Pb exposure delayed the neurite outgrowth and reduced the survival rate of cultured hippocampal neurons at different time-points. Together, our results demonstrate that developmental low-level Pb exposure can attenuate the expression of all three major NCAM isoforms, which may contribute to the observed Pb-mediated neurotoxicity.
authors.affiliation: Department of Preventive Medicine, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China. huqsh@mail.sysu.edu.cn
authors.forename: Qiansheng
authors.initials: Q
authors.lastname: Hu
authors.forename: Hongjun
authors.initials: H
authors.lastname: Fu
authors.forename: Hong
authors.initials: H
authors.lastname: Song
authors.forename: Tieling
authors.initials: T
authors.lastname: Ren
authors.forename: Liquan
authors.initials: L
authors.lastname: Li
authors.forename: Liuqing
authors.initials: L
authors.lastname: Ye
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Shengzhang
authors.initials: S
authors.lastname: Dong
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D057809:HEK293 Cells; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007854:Lead / Q000008:administration & dosage* / Q000633:toxicity*; D019006:Neural Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms; D007854:Lead