title: Lead-induced ER calcium release and inhibitory effects of methionine choline in cultured rat hippocampal neurons.
abstract: Lead, a ubiquitous neurotoxicant, can result in learning and memory dysfunction. Long term potentiation in the hippocampus, a potential neural substrate for learning and memory, is thought to be linked to calcium-triggered intracellular events. In this study, laser scanning confocal microscopy was used to examine the effects of Pb(2+) on intracellular and endoplasmic reticulum free calcium concentration ([Ca(2+)](i) and [Ca(2+)](ER)) in cultured neonatal rat hippocampal neurons and their possible antagonism by methionine choline; understanding these effects would help explain the lead-induced cognitive and learning dysfunction and explore efficient safety and relief strategies. The results showed that Pb(2+) increased [Ca(2+)](i) and decreased [Ca(2+)](ER) linearly in a time- and concentration-dependant manner, and Pb(2+) addition after the applying of a ryanodine receptor (RyR) antagonist and an inositol-1,4,5-triphosphate receptor (IP(3)R) antagonist did not increase [Ca(2+)](i). The addition of 10, 20, or 40 mmol/L methionine choline simultaneously with addition of 10 μmol/L Pb(2+) decreased [Ca(2+)](i) in Ca(2+)-free culture medium by 39.0%, 66.0%, and 61.6%, respectively, in a concentration-dependant manner in a certain dose range. Our results suggest that Pb(2+) induces ER calcium release to increase the resting [Ca(2+)](i); and methionine choline inhibit this increase in [Ca(2+)](i).
authors.affiliation: Department of Occupational Health and Toxicology, School of Public Health, Nanchang University, BaYi Road 461, Nanchang 330006, PR China. gq_fan@163.com
authors.forename: Guangqin
authors.initials: G
authors.lastname: Fan
authors.forename: Fankun
authors.initials: F
authors.lastname: Zhou
authors.forename: Chang
authors.initials: C
authors.lastname: Feng
authors.forename: Fengyun
authors.initials: F
authors.lastname: Wu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Ye
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.forename: Fen
authors.initials: F
authors.lastname: Lin
authors.forename: Ji
authors.initials: J
authors.lastname: Yan
authors.forename: Yanshu
authors.initials: Y
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Bi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002794:Choline / Q000008:administration & dosage*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D008715:Methionine / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D007854:Lead; D008715:Methionine; D002794:Choline; D002118:Calcium