Inhibition of vitamin B12 metabolism by OH-cobalamin c-lactam in rat oligodendrocytes in culture: a model for studying neuropathy due to vitamin B12 deficiency.
Vitamin B12 is implicated in methylation processes. Myelin basic protein is methylated on one arginine group. A defect in methylation could produce an unstable protein, leading to neurological disorders. In order to study myelin basic protein, we have developed the cultures of newborn rat oligodendrocytes in vitamin B12-depleted medium. As these cells do not grow without serum, vitamin B12 is always present. We overcame this problem by using OH-cobalamin c-lactam, an antagonist of B12. To ensure that the system was vitamin B12 deficient, we measured the concentrations of homocysteine and methylmalonic acid whose accumulations reflect a vitamin B12 deficiency. Methylmalonic acid was measured by mass spectrometry and homocysteine by HPLC. We obtained a powerful model for studying the influence of B12 deficiency on the synthesis of myelin compounds.
Sponne
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INSERM U. 308, Micronutriments et Système Nerveux Central, Faculté de Médecine, BP 184 Avenue de la Forêt de Haye, 54505 Cédex, Vandoeuvre, France.
Gaire
D
D
Stabler
S P
SP
Droesch
S
S
Barbé
F M
FM
Allen
R H
RH
Lambert
D A
DA
Nicolas
J P
JP
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D008764:Methylmalonic Acid / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000494:pharmacology*; D014806:Vitamin B 12 Deficiency / Q000150:complications / Q000378:metabolism* / Q000473:pathology*
D017077:Culture Media, Conditioned; C071541:hydroxycobalamin(c-lactam); D006710:Homocysteine; D008764:Methylmalonic Acid; D014805:Vitamin B 12