Abnormal O-GlcNAcylation of Pax3 Occurring from Hyperglycemia-Induced Neural Tube Defects Is Ameliorated by Carnosine But Not Folic Acid in Chicken Embryos.
Neural tube defects (NTDs) are among the most common of the embryonic abnormalities associated with hyperglycemic gestation. In this study, the molecular mechanisms of embryonic neurogenesis influenced by hyperglycemia was investigated using chicken embryo models. High-concentration glucose was administered into chicken eggs and resulted in increased plasma and brain tissue glucose, and suppressed expression of glucose transporters (GLUTs). The rate of NTD positively correlated with hyperglycemia. Furthermore, abnormally increased O-GlcNAcylation, a nutritionally responsive modification, of the key neural tube marker Pax3 protein led to the loss of this protein. This loss was not observed in a folate-deficiency NTD induced by methotrexate. Carnosine, an endogenous dipeptide, showed significant recovery effects on neural tube development. In contrast, folic acid, a well-known periconceptional agent, surprisingly showed relatively minimal effect. Higher expression levels of the Pax3 protein were found in the carnosine-treated groups, while lower expression levels were found in folic acid groups. Furthermore, the abnormal O-GlcNAcylation of the Pax3 protein was restored by carnosine. These results suggest new insights into using endogenous nutrients for the protection of embryonic neurodevelopment affected by diabetes gestation. The abnormal excessive O-GlcNAcylation of Pax3 may be responsible for the neural tube defects associated with hyperglycemia.
['Tan|Rui-Rong|RR|', 'Li|Yi-Fang|YF|', 'Zhang|Shi-Jie|SJ|', 'Huang|Wen-Shan|WS|', 'Tsoi|Bun|B|', 'Hu|Dan|D|', 'Wan|Xin|X|', 'Yang|Xuesong|X|', 'Wang|Qi|Q|', 'Kurihara|Hiroshi|H|', 'He|Rong-Rong|RR|']
D000215:Acylation D000818:Animals D002336:Carnosine D002642:Chick Embryo D004305:Dose-Response Relationship, Drug D005492:Folic Acid D005947:Glucose D006943:Hyperglycemia D009436:Neural Tube Defects D000072041:PAX3 Transcription Factor
O-GlcNAcylation Pax3 Neural tube defects Carnosine Folic acid Hyperglycemia