Contributions
Abstract: EP1512
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 20 Repairing mechanisms
Receptor tyrosine kinases of the TAM (Tyro3, Axl, Mer) subfamily are expressed in the CNS, and a number of reports have shown that their activation via their common ligand Gas6 has a positive effect on (re)myelination as well as on glial cell development. Gas6 undergoes post-translational processing, and thereby functional activation, through vitamin K (Vit K)-dependent gamma-carboxylation of a number of glutamic acid residues within the protein. However, little is currently known about the expression of Gas6 in the brain or the factors that regulate its expression and/or its post-translational activation state. Such knowledge can lend support to strategies aimed at activating Gas6-TAM signalling in the brain as a means of promoting remyelination in MS.
The study presented here is aimed at investigating the effects of various candidate molecules on the levels of endogenous Gas6 gene expression in the mouse brain. Molecules were administered in vivo or in vitro using an organotypic brain slice culture model. C57/BL6 mice were injected with Vit K1 intraperitoneally, and after 24 hours samples from brain and liver were harvested for gene and protein expression analyses. In addition, cultured brain slices from mice at postnatal day 8-12 were treated with the following agents: Vit K1, Vit K2, Vit D3, dexamethasone and IL-10. Samples were incubated with the tissues for four days, and tissues were analysed by qPCR for gene expression, and in addition the culture medium was assayed by ELISA for presence of released Gas6 protein. Results so far show that Vit D3 caused an increase in expression of the gas6 gene in cultured mouse brain tissues. In addition, western blot analysis showed that in vivo administration of Vit K1 to mice caused an increase in the levels of gamma carboxylated proteins in the liver; brain analysis is ongoing.
These results show that Vit K administration can stimulate gamma-carboxylation of Vit K-dependent proteins in vivo and, furthermore, that the steroid hormone Vit D3 is able to upregulate Gas6 expression in brain tissue in vitro. Therefore, Vit D3 could be a potential promoter of remyelination during the course of MS through induction of endogenous Gas6-TAM signalling in the CNS.
Disclosure: Salman Goudarzi, Nadide Aydin, Sassan Hafizi: nothing to disclose
Abstract: EP1512
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 20 Repairing mechanisms
Receptor tyrosine kinases of the TAM (Tyro3, Axl, Mer) subfamily are expressed in the CNS, and a number of reports have shown that their activation via their common ligand Gas6 has a positive effect on (re)myelination as well as on glial cell development. Gas6 undergoes post-translational processing, and thereby functional activation, through vitamin K (Vit K)-dependent gamma-carboxylation of a number of glutamic acid residues within the protein. However, little is currently known about the expression of Gas6 in the brain or the factors that regulate its expression and/or its post-translational activation state. Such knowledge can lend support to strategies aimed at activating Gas6-TAM signalling in the brain as a means of promoting remyelination in MS.
The study presented here is aimed at investigating the effects of various candidate molecules on the levels of endogenous Gas6 gene expression in the mouse brain. Molecules were administered in vivo or in vitro using an organotypic brain slice culture model. C57/BL6 mice were injected with Vit K1 intraperitoneally, and after 24 hours samples from brain and liver were harvested for gene and protein expression analyses. In addition, cultured brain slices from mice at postnatal day 8-12 were treated with the following agents: Vit K1, Vit K2, Vit D3, dexamethasone and IL-10. Samples were incubated with the tissues for four days, and tissues were analysed by qPCR for gene expression, and in addition the culture medium was assayed by ELISA for presence of released Gas6 protein. Results so far show that Vit D3 caused an increase in expression of the gas6 gene in cultured mouse brain tissues. In addition, western blot analysis showed that in vivo administration of Vit K1 to mice caused an increase in the levels of gamma carboxylated proteins in the liver; brain analysis is ongoing.
These results show that Vit K administration can stimulate gamma-carboxylation of Vit K-dependent proteins in vivo and, furthermore, that the steroid hormone Vit D3 is able to upregulate Gas6 expression in brain tissue in vitro. Therefore, Vit D3 could be a potential promoter of remyelination during the course of MS through induction of endogenous Gas6-TAM signalling in the CNS.
Disclosure: Salman Goudarzi, Nadide Aydin, Sassan Hafizi: nothing to disclose