title: Involvement of decreased glutamate receptor subunit GluR2 expression in lead-induced neuronal cell death.
abstract: Lead is known to induce neurotoxicity, particularly in young children, and GluR2, an AMPA-type glutamate receptor subunit, plays an important role in neuronal cell survival. Therefore, we hypothesized that altered GluR2 expression plays a role in lead-induced neuronal cell death. To test this idea, we investigated the effect of exposure to 5 and 20 µM lead for 1-9 days on the viability and GluR2 expression of primary-cultured rat cortical neurons. The number of trypan-blue stained cells was increased by exposure to 5 µM lead for 9 days or 20 µM lead for 7-9 days, and LDH release was increased after exposure to 20 µM lead for 9 days. GluR2 expression was reduced by exposure to 5-100 µM lead, but not 0.1-1 µM lead, for 9 days. Immunocytochemistry also confirmed that GluR2 expression was decreased in the presence of lead. Application of 50 ng/ml brain-derived neurotrophic factor (BDNF) led to a recovery of lead-induced neuronal cell death, accompanied with increased GluR2 expression. Our results suggest that long-term exposure to lead induces neuronal cell death, in association with a decrease of GluR2 expression.
authors.affiliation: Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Ishida
authors.forename: Yaichiro
authors.initials: Y
authors.lastname: Kotake
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Miyara
authors.forename: Kaori
authors.initials: K
authors.lastname: Aoki
authors.forename: Seigo
authors.initials: S
authors.lastname: Sanoh
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Kanda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics*; D007854:Lead / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018091:Receptors, AMPA; D007854:Lead; C104722:glutamate receptor ionotropic, AMPA 2