title: Expression profiling of Ca(2+)/calmodulin-dependent signaling molecules in the rat dorsal and ventral hippocampus after acute lead exposure.
abstract: The septal and temporal poles of the hippocampus differ markedly in their anatomical organization, but whether these distinct regions exhibit differential neurochemical profiles underlying lead (Pb(2+)) neurotoxicity remains to be determined. In the present study, we examined changes in the expression of Ca(2+)/calmodulin-dependent enzymes, including calpain, calcineurin, phospho-CaMKII (Thr286) and neuronal nitric oxide synthase (nNOS), in the rat dorsal and ventral hippocampus (DH and VH) after acute Pb(2+) exposure. Five days after Pb(2+) exposure, we observed constitutively active forms of calcineurin (45 kDa and 48 kDa) in ventral portions of the hippocampus, a result consistent with the observed calpain activation that is indicated by the breakdown of spectrin in this region. Our data demonstrate that nNOS expression is significantly higher in the ventral region of the hippocampus when compared to the dorsal region, whereas phosphorylation of CaMKII (Thr286) is less pronounced in the ventral portion of the hippocampus and more pronounced in dorsal regions after acute Pb(2+) exposure. Thus, it appears likely that the ventral region of hippocampus is more vulnerable to the neurotoxic effects of Pb(2+) than the dorsal region. Taken together, the present data suggest that acute lead exposure leads to differential expression patterns of Ca(2+)/calmodulin-dependent enzymes along the dorsoventral axis of the hippocampus.
authors.affiliation: Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou 310058, China.
authors.forename: Gen-sheng
authors.initials: GS
authors.lastname: Zhang
authors.forename: Wei-feng
authors.initials: WF
authors.lastname: Ye
authors.forename: Rong-rong
authors.initials: RR
authors.lastname: Tao
authors.forename: Ying-mei
authors.initials: YM
authors.lastname: Lu
authors.forename: Guo-fang
authors.initials: GF
authors.lastname: Shen
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Ji-yun
authors.initials: JY
authors.lastname: Huang
authors.forename: Yue-long
authors.initials: YL
authors.lastname: Ji
authors.forename: Feng
authors.initials: F
authors.lastname: Han
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020013:Calcium Signaling / Q000187:drug effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000032:analysis / Q000378:metabolism*; D002154:Calpain / Q000032:analysis / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D007854:Lead / Q000633:toxicity*; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D007854:Lead; D052248:Nitric Oxide Synthase Type I; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002154:Calpain