Diminished degradation of myelin basic protein by anti-sulfatide antibody and interferon-gamma in myelin from glia maturation factor-deficient mice.
In this study we show the effect of anti-sulfatide (RmAb) antibodies and inflammatory cytokines, TNF-alpha and IFN-gamma 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 17.5kDa isoforms of MBP in WT myelin treated with RmAb or IFN-gamma. In contrast, MBP degradation in isolated myelin from GMF-KO mice remained unaffected following treatment with RmAb, IFN-gamma, or GM-CSF. Neither the 14kDa isoform of MBP nor proteolipid protein (PLP) showed an elevated degradation compared to controls. A virtual absence of GM-CSF, TNF-alpha and IFN-gamma 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 beta-tubulin in a sucrose density gradient myelin-axolemmal 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-gamma.
Menon
Krishnakumar
K
Veterans Affair Medical Center, Iowa City, IA, United States.
Wu
Yanghong
Y
Haas
Joel
J
Sahu
Shailendra K
SK
Yang
Baoli
B
Zaheer
Asgar
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D020904:Glia Maturation Factor / Q000172:deficiency*; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000378:metabolism*; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000187:drug effects*; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009444:Neuritis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000276:immunology*
D000906:Antibodies; D002614:Chelating Agents; D020904:Glia Maturation Factor; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D013433:Sulfoglycosphingolipids; D004533:Egtazic Acid; D007371:Interferon-gamma; D002118:Calcium