Diminished degradation of myelin basic protein by anti-sulfatide antibody and interferon-γ in myelin from glia maturation factor-deficient mice

Abstract

In this study we show the effect of anti-sulfatide (RmAb) antibodies and inflammatory cytokines, TNF-α and IFN-γ in inducing myelin basic protein (MBP) degradation in myelin isolated from control wild type (WT) and glia maturation factor (GMF)-deficient (GMF-KO) mice. GMF was not detected in isolated myelin from WT and GMF-KO mice although it is present in brains of WT mice. Our results show that calcium dependent neutral protease activity caused significantly elevated degradation of 18.5 and/or 17.5 kDa isoforms of MBP in WT-myelin treated with RmAb or IFN-γ. In contrast, MBP degradation in isolated myelin from GMF-KO mice remained unaffected following treatment with RmAb, IFN-γ, or GM-CSF. Neither the 14 kDa isoform of MBP or proteolipid protein (PLP) showed an elevated degradation compared to controls. A virtual absence of GM-CSF, TNF-α and IFN-γ in GMF-KO brain compared to WT was also evident when the animals were challenged with MOG 35-55. Additionally, the myelin from GMF-KO mice showed difference in distribution of myelin oligodendrocyte glycoprotein (MOG) and β-tubulin in a sucrose density gradient myelinaxolemmal fractions compared to WT. Taken together, our data suggests a role for GMF in the biochemical organization of myelin and thereby its effect on MBP degradation induced by RmAb and IFN-γ.

Glia maturation factor overexpression in neuroblastoma cells activates glycogen synthase kinase-3β and caspase-3

“…We reported that the overexpression of GMF in astrocytes leads to the destruction of primary oligodendrocytes, the myelin-forming cells in the central nervous system, by interactions between astrocytes, microglia, and oligodendrocytes. These results suggested a novel pathway of GMF initiated cytotoxicity of brain cells, and implicated its involvement in the pathogenesis of inflammatory demyelinating diseases of the central nervous system such as multiple sclerosis/ experimental autoimmune encephalomyelitis (Menon et al, 2007;Zaheer et al, 2007a;Zaheer et al, 2007b;Zaheer et al, 2007c;Zaheer et al, 2007d). In the present report we show that the overexpression of GMF in neuroblastoma N18 cells directly induces caspase-dependent apoptosis mediated by GSK-3β activation.…”

Reovirus type-2–triggered autoimmune cholangitis in extrahepatic bile ducts of weanling DBA/1J mice

“…The BN-77 Reo-2 strain, isolated from bovine diarrheal matter, was grown on HmLu-1 cells as described previously (33). One-day-old mice were i.p.…”

Destruction of Salivary and Lacrimal Glands by Th1-Polarized Reaction in a Model of Secondary Sjögren’s Syndrome in Lupus-Prone Female NZB × NZWF1 Mice

“…This mixture was used for assay of IL-4, IFN-γ, and GAPDH mRNAs. The primers used for these genes (Table 1) [ [23][24][25] were made based on mouse sequences to amplify the fragments spanning exon/intron junction.…”