title: Acute phase expression pattern of ZnTs, LC3, and beclin-1 in rat Hippocampus and its regulation by 3-methyladenine following recurrent neonatal seizures.
abstract: It has been reported that autophagy and zinc transporters (ZnTs) both play the key roles in excitotoxicity, which is associated with cognitive deficits following developmental seizures. However, the influence of autophagy on acute phase ZnTs expression has never been studied. The present study sought to investigate the contribution of an autophagy inhibitor (3-methyladenine, 3-MA) on the regulation of ZnTs, microtubule-associated protein 1A/1B light chain 3 (LC3), and beclin-1 expression in rat hippocampus following recurrent neonatal seizures. We examined the expression of ZnT1~ZnT3, LC3, and beclin-1 at 1.5, 3, 6, and 24 h after the last seizures using real-time RT-PCR and Western blot methods, respectively. The results showed that there were upregulated expressions of ZnT-1, ZnT-2, LC3, and beclin-1 of RS group. Pretreatment with 3-MA remarkably attenuated seizure-induced ZnT-1, ZnT-2, LC3, and beclin-1 increase. Additionally, linear correlations could be observed between LC3-Beclin1, LC3-ZnT-2, Beclin1-ZnT2, Beclin1-ZnT3, and among ZnT1~ZnT3 in control group, while the linear correlations could be observed between LC3-Beclin1, Beclin1-ZnT2, and Beclin1-ZnT3 in RS group. These results demonstrate, for the first time, that there exists an interaction of Zn(2+) with autophagic signals that are immediately activated in hippocampus after recurrent neonatal seizures, which might play a key role in neonatal seizure-induced excitotoxicity.
authors.affiliation: Neurology Laboratory, Soochow University Affiliated Children's Hospital, Laboratory of Aging and Nervous Diseases, Soochow University, No 303, Jingde Road, 215003 Suzhou, China. nyr2000@yeah.net
authors.forename: Hong
authors.initials: H
authors.lastname: Ni
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.forename: Yong
authors.initials: Y
authors.lastname: Gong
authors.forename: Lu-Yang
authors.initials: LY
authors.lastname: Tao
authors.forename: Xi-Ru
authors.initials: XR
authors.lastname: Wu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000225:Adenine; D027682:Cation Transport Proteins; D008869:Microtubule-Associated Proteins; C526109:Anxa3 protein, rat; C503697:zinc transporter 3, rat; C092392:Slc30a1 protein, rat; C025946:3-methyladenine