title: Abnormal O-GlcNAcylation of Pax3 Occurring from Hyperglycemia-Induced Neural Tube Defects Is Ameliorated by Carnosine But Not Folic Acid in Chicken Embryos.
abstract: 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.
authors.affiliation: College Pharmacy, Jinan University, Guangzhou, 510632, China.|International Center for Translational Chinese Medicine, Sichuan TCM Science Academy, Chengdu, 610041, China.
authors.forename: Rui-Rong
authors.initials: RR
authors.lastname: Tan
authors.affiliation: College Pharmacy, Jinan University, Guangzhou, 510632, China.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Li
authors.affiliation: College Pharmacy, Jinan University, Guangzhou, 510632, China.|Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Zhang
authors.affiliation: College Pharmacy, Jinan University, Guangzhou, 510632, China.
authors.forename: Wen-Shan
authors.initials: WS
authors.lastname: Huang
authors.affiliation: College Pharmacy, Jinan University, Guangzhou, 510632, China.
authors.forename: Bun
authors.initials: B
authors.lastname: Tsoi
authors.affiliation: College Pharmacy, Jinan University, Guangzhou, 510632, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: College Pharmacy, Jinan University, Guangzhou, 510632, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wan
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou, 510632, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College Pharmacy, Jinan University, Guangzhou, 510632, China.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurihara
authors.affiliation: College Pharmacy, Jinan University, Guangzhou, 510632, China. rongronghe@jnu.edu.cn.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: He
mesh_terms: D000215:Acylation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002336:Carnosine / Q000494:pharmacology / Q000627:therapeutic use*; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005492:Folic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005947:Glucose / Q000633:toxicity*; D006943:Hyperglycemia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D009436:Neural Tube Defects / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D000072041:PAX3 Transcription Factor / Q000378:metabolism*
chemical_list: D000072041:PAX3 Transcription Factor; D002336:Carnosine; D005492:Folic Acid; D005947:Glucose
keywords: Carnosine; Folic acid; Hyperglycemia; Neural tube defects; O-GlcNAcylation; Pax3