title: Metallothionein I+II expression as an early sign of chronic relapsing experimental autoimmune encephalomyelitis in rats.
abstract: Metallothioneins (MTs) are small, cysteine-rich proteins which have been implicated in various forms of stress providing cytoprotective action against oxidative injury, DNA damage and apoptosis. Owing to their high affinity for physiological metals, such as zinc and copper MTs are also critical components of regulatory proteins involved in cell growth and multiplication, as well as in the maintenance of immune homeostasis. To elucidate the role of MTs in the pathomechanisms of autoimmune CNS disorders we estimated the expression of MT I+II proteins and the content of free Zn ions in the brain, spinal cord and in the liver early in the course of chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) pathogenesis, i.e. before the onset of any clinical symptoms. Disease was induced in the genetically susceptible Dark Agouti (DA) rats by subcutaneous injection of bovine brain homogenate in CFA. Control animals were treated with CFA alone. The data, obtained by immuno-histochemistry and in situ fluorescent labeling of free zinc ions, have shown that in the presymptomatic phase of CR-EAE (on the seventh postimmunization day) MTs I+II were markedly upregulated in the cells that form blood-brain and blood-cerebrospinal fluid barriers, as well as in the cerebellar parenchyma and hippocampal dentate gyri. Furthermore, we found that the liver also becomes a site of extensive MTs I+II synthesis shortly after immunization. Simultaneously, tissue content of free zinc ions increased at the sites of MTs induction, reflecting their antioxidative activity. The data, described in this paper point to regulatory and neuroprotective role of MTs in the pathogenesis of CR-EAE.
authors.affiliation: Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia. Hrvoje.Jakovac@medri.hr
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Jakovac
authors.forename: Marin
authors.initials: M
authors.lastname: Tota
authors.forename: Damir
authors.initials: D
authors.lastname: Grebic
authors.forename: Tanja
authors.initials: T
authors.lastname: Grubic-Kezele
authors.forename: Vesna
authors.initials: V
authors.lastname: Barac-Latas
authors.forename: Ines
authors.initials: I
authors.lastname: Mrakovcic-Sutic
authors.forename: Cedomila
authors.initials: C
authors.lastname: Milin
authors.forename: Biserka
authors.initials: B
authors.lastname: Radosevic-Stasic
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D015854:Up-Regulation; D015032:Zinc / Q000378:metabolism
chemical_list: C491055:Mt2A protein, rat; D008668:Metallothionein; D015032:Zinc