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Pregled bibliografske jedinice broj: 478968

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Autori: Jakovac, Hrvoje; Tota, Marin; Grebić, Damir; Grubić-Kezele, Tanja; Barac-Latas, Vesna; Mrakovčić-Šutić, Ines; Milin, Čedomila; Radošević-Stašić, Biserka
Naslov: Metallothioneins I+II expression and tissue metals kinetics during chronic relapsing experimental autoimmune encephalomyelitis in rats
( Metallothioneins I+II expression and tissue metals kinetics during chronic relapsing experimental autoimmune encephalomyelitis in rats )
Izvornik: The primeval life-generating molecules, therapeutic and ageing-reversing properties / Pierpaoli, Walter and Mehta, Linda (ur.). - Gordola, Switzerland : Interbion Foundation for Basic Biomedical Research , 2010. 24-24.
Skup: Fifth Stromboli Conference on Aging and Cancer
Mjesto i datum: Stromboli, Italija, 13-19.06.2010.
Ključne riječi: Metallothioneins I+II; CR-EAE; brain; spinal cord; liver; DA rats
( Metallothioneins I+II; CR-EAE; brain; spinal cord; liver; DA rats )
Metallothioneins (MTs) are small, cysteine-rich proteins that 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 multiple regulatory proteins involved in cell growth and multiplication, as well as in the maintenance of immune homeostasis, affecting the functions of immune cells, TLR signaling, upregulation of co-stimulatory molecules on antigen-presenting cells (APC) and the production of pro-inflammatory cytokines. Therefore, their expression may be induced through several response elements in the MT gene promoter: 1) metal response elements, which are activated by the metal-responsive transcription factor-1 after zinc occupancy, 2) glucocorticoid responsive elements activated by stress, 3) elements activated by signal transducers and activators of transcription proteins through cytokine signaling and 4) the antioxidant (or electrophile) response element (ARE) activated in response to redox status. The extensive data show that these proteins confer a protective effect also within the mammalian CNS, where the MT I+II expression dramatically increases in response to many types of CNS and spinal cord (SC) injury or ischemia, as well as in senescence and in several neurodegenerative and autoimmune diseases. To obtain an insight into the changes of MT-trace metal circuit during the development of an autoimmune disease, in this study we correlated the expression of MT I+II in the brain, SC and liver with total zinc and copper content in these organs, during clinically different stages of chronic relapsing (CR) experimental autoimmune encephalomyelitis (EAE): 1) in early, asymptomatic phase (on the 7th post-immunization day ; 2) during periods of attacks (on the 12th and the 22nd day), and 3) during the period of remissions of EAE (on the 18th and the 28th day). Disease was induced in the genetically susceptible DA rats by subcutaneous injection of encephalitogen (bovine brain homogenate in CFA). Rats in the control groups were treated only with CFA. MTs I+II and tissue metals were evaluated by immunocytochemistry and by inductively coupled plasma spectrometry, respectively. Additionally, in the asymptomatic stage of EAE the free intracellular Zn2+ content in the brain and SC were visualized by Zinquin (a selective Zn 2+ fluorophore). The data revealed an early upregulation of MTs and free Zn2+ content in the brain and SC in preclinical phase of disease and their marked overexpression during both attacks at sites of invasion of myelin-reactive T cells into CNS and their reactivation on local APC (on endothelial cells, ventricular subependyma, microglia/macrophages and astroglial cells around the ventricle walls and blood vessels), as well as in the molecular layer of cerebellum, in subgranular layer of gyrus dentatus, and on several neurons and oligodendrocytes in SC. Simultaneously, increased the content of free Zn2+ at these sites and the total Zn2+ content in the cervical SC. Furthermore, during attacks in the liver markedly arose the expression of MT I+II and tissue concentrations of total zinc and copper. The data point to neuroprotective role of MTs and to important regulatory role hepatic MTs in pathogenesis of EAE (Supported by grant 0621341-1337 from Croatian Ministry of Science). 
Vrsta sudjelovanja: Pozvano
Vrsta prezentacije u zborniku: Sažetak
Vrsta recenzije: Međunarodna recenzija
Projekt / tema: 062-0621341-1337
Izvorni jezik: eng
Kategorija: Znanstveni
Znanstvena područja:
Temeljne medicinske znanosti
Upisao u CROSBI: (, 23. Kol. 2010. u 14:58 sati

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