title: The increase in zinc levels and upregulation of zinc transporters are mediated by nitric oxide in the cerebral cortex after transient ischemia in the rat.
abstract: The transient occlusion of cerebral arteries causes an increase in zinc levels in the brain, which is associated with a production of nitric oxide (NO). The types of zinc transporters (ZnT) involved in zinc homeostasis in the cerebral cortex after hypoxia-ischemia are not completely known. We studied the effect of the transient occlusion (10 min) of the common carotid artery (CCA) on NO-induced zinc levels, ZnT mRNA expression, and cell-death markers in the cerebral cortex-hippocampus of the rat. Nitrites, zinc, and lipoperoxidation were quantified by colorimetric methods, ZnT expression was determined by RT-PCR, caspase-3 by ELISA and immunohistochemistry, and histopathological alterations by H&E staining. After restoration of the blood flow, the basal levels of NO and zinc increased in a biphasic manner over time, but the peaks of NO levels appeared earlier (2 h and 24 h) than those of zinc (6 h and 36 h). Upregulation of ZnT1, ZnT2, and ZnT4 mRNAs was determined after 8-h postreperfusion, but ZnT3 RNA levels were unaffected. Lipoperoxidation and caspase-3 levels were also increased, and necrosis and apoptosis were present at 24 h postreperfusion. All the effects determined were prevented by l-nitro-arginine methyl ester injected 1 h before the occlusion of the CCA. Our results suggest that the upregulation of ZnT1, ZnT2, and ZnT4 was to decrease the cytosolic zinc levels caused by NO after transient occlusion of the CCA, although this was unable to lead to physiological levels of zinc and to prevent cell damage in the cerebral cortex-hippocampus of the rat.
authors.affiliation: Area de Bioquímica y Biología Molecular, Facultad de Ciencias químicas, BUAP. 14 sur y Av. San Claudio, 72570, Puebla, Pue. México.
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Alonso
authors.forename: Daniel
authors.initials: D
authors.lastname: Martinez-Fong
authors.forename: Nidia G
authors.initials: NG
authors.lastname: Pazos-Salazar
authors.forename: Eduardo
authors.initials: E
authors.lastname: Brambila
authors.forename: Juan A
authors.initials: JA
authors.lastname: Gonzalez-Barrios
authors.forename: Alejandro
authors.initials: A
authors.lastname: Mejorada
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Flores
authors.forename: Lourdes
authors.initials: L
authors.lastname: Millan-Perezpeña
authors.forename: Hector
authors.initials: H
authors.lastname: Rubio
authors.forename: Bertha A
authors.initials: BA
authors.lastname: Leon-Chavez
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology; D015032:Zinc / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C491596:Slc30a4 protein, rat; C503697:zinc transporter 3, rat; C092392:Slc30a1 protein, rat; D009569:Nitric Oxide; D053148:Caspase 3; D015032:Zinc