IL-10 Gene Knockout Reduces the Expression of mGlu Receptor 1a-b and Decreases the Glutamate-Dependent Production of Nitric OxideReportar como inadecuado




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IL-10 provides trophic and survival effects directly on neurons, promotes axonal outgrowth, and stimulates neuroregeneration. In this study, we analyzed the activities of arginase and nitric oxide synthase NOS in synaptoneurosomes derived from brain cortex of C57BL-6 IL-10 gene-knockout KO and wild-type Wt mice and determined that the synaptoneurosomes derived from KO mice present lower arginase II activity and lower spermine content than those derived from Wt mice, whereas the basal NOS activity in the KO synaptoneurosomes was higher than that observed in the control synaptoneurosomes. Moreover, our results indicate that the plasma membranes isolated from the KO mice brain exhibit significantly lower spermine-induced enhancement of 3H MK-801 binding than the plasma membranes from the brain of Wt mice. Glutamate increases the production of nitric oxide NO in Wt synaptoneurosomes in a dose-dependent manner, whereas in the KO synaptoneurosomes, this amino acid does not affect the synthesis of NO. The glutamate-dependent acceleration of NO synthesis in Wt synaptoneurosomes was abrogated by LY367385, an antagonist of mGluR1a-b. The western blot analysis of the synaptoneurosomal proteins demonstrates that the expression of the subunits of NMDAR NMDAR2A and NMDAR2B, the level of NMDAR-bound nNOS and the expression of iNOS are not changed in KO mice and that only the level of mGluR1a-b is markedly reduced in the synaptoneurosomes of KO mice. We conclude that a neuroprotective and neuroregenerative property of IL-10, in addition to its effects on polyamine metabolism and the spermine-dependent modulation of NMDAR, may involve the regulation of mGluR1a-b expression.

KEYWORDS

IL-10, Polyamine Biosynthesis, Nitric Oxide, Metabotropic Glutamate Receptor

Cite this paper

Koriauli, S. , Barbakadze, T. , Natsvlishvili, N. , Dabrundashvili, N. , Kvaratskhelia, E. and Mikeladze, D. 2014 IL-10 Gene Knockout Reduces the Expression of mGlu Receptor 1a-b and Decreases the Glutamate-Dependent Production of Nitric Oxide. Journal of Biomedical Science and Engineering, 7, 1019-1029. doi: 10.4236-jbise.2014.713099.





Autor: Sopiko Koriauli1, Tamar Barbakadze1,2, Nino Natsvlishvili1,2, Nino Dabrundashvili3, Eka Kvaratskhelia3, David Mikeladze1,2*

Fuente: http://www.scirp.org/



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