engleski

Metallothioneins I and II expression in rat strains with genetically different susceptibility to experimental autoimmune encephalomyelitis

Albino Oxford rats, compared to the Dark Agouti strain, exhibit lower susceptibility to the induction of EAE. Mechanisms include the differences in peripheral response to immunization and those linked with the CNS milieu, which contribute to limit the injury. In the search for factors related to these differences, we estimated the expression pattern of the cysteine rich proteins-metallothioneins I and II that maintain the metal ion homeostasis and have marked anti-inflammatory and neuroprotective properties. Rats were immunized with bovine brain homogenate emulsified in CFA or with CFA only. On days 7 and 12 after immunization MTs mRNA and protein expression, as well as the tissue concentrations of Zn+2, Cu+2 and Fe+2 were estimated in the liver, brain and spinal cord by real time PCR, immunohistochemistry and inductively coupled plasma spectrometry, respectively. AO rats did not shown any clinical sign of EAE, but increased MTs protein expression was detected in the brain upon immunization, similarly to diseased DA rats. Transcriptional activation of MTs was, however, much slower in AO than in DA rats, in which mRNA of MTs augmented first in hepatic and hippocampal tissues (on the 7th p.i. day) and then in the cerebellum (on the 12th p.i. day). In contrast, constitutive MT I and II gene expression in the liver of intact AO rats was found to be greater than that in DA rats. Furthermore, intact DA rats had significantly higher concentrations of Cu+2, Zn+2 and Fe+2 in spinal cords, while higher levels of these metals accumulated in their liver and brain during the paralytic attack. The data point to differences between constitutive and induced MT I and II gene expression in EAE-resistant and EAE-prone rats both in the liver and in the organs that were damaged by the autoimmune attack, implying the participation of mechanisms that maintain tissue metal homeostasis and ensure protection against oxidative and nitrosative injuries in biological systems.

experimental autoimmune encephalomyelitis; AO and DA rats

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