Abnormal O-GlcNAcylation of Pax3 Occurring from Hyperglycemia-Induced Neural Tube Defects Is Ameliorated by Carnosine But Not Folic Acid in Chicken Embryos
Abnormal O-GlcNAcylation of Pax3 Occurring from Hyperglycemia-Induced Neural Tube Defects Is Ameliorated by Carnosine But Not Folic Acid in Chicken Embryos
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鸡胚胎中的肌肽可以改善高血糖引起的神经管缺陷引起的 Pax3 的异常 O-GlcNAc 酰化，但不能改善叶酸
DOI：
10.1007/s12035-015-9581-8
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发表时间：
2015
影响因子：
5.1
通讯作者：
He Rong-Rong
中科院分区：
文献类型：
--
作者：
Tan Rui-Rong;Li Yi-Fang;Zhang Shi-Jie;Huang Wen-Shan;Tsoi Bun;Hu Dan;Wan Xin;Yang Xuesong;Wang Qi;Kurihara Hiroshi;He Rong-Rong
神经管缺陷（NTDs）是妊娠高血糖相关的最常见的胚胎异常之一。本研究以鸡胚为模型，探讨高血糖对胚胎神经发生影响的分子机制。高浓度葡萄糖灌胃鸡卵可导致血浆和脑组织葡萄糖升高，并抑制葡萄糖转运蛋白（GLUT）的表达。NTD发生率与高血糖呈正相关。此外，关键神经管标志物Pax 3蛋白的异常增加的O-GlcNAc化（营养响应性修饰）导致该蛋白的丢失。在甲氨蝶呤诱导的叶酸缺乏NTD中未观察到这种损失。肌肽是一种内源性二肽，对神经管发育有明显的恢复作用。相反，叶酸，一种众所周知的围受孕期药物，令人惊讶地显示出相对最小的作用。在肌肽处理组中发现较高的Pax 3蛋白表达水平，而在叶酸组中发现较低的表达水平。此外，Pax 3蛋白的异常O-GlcNAc化被肌肽恢复。这些结果为利用内源性营养素保护妊娠期糖尿病影响的胚胎神经发育提供了新的见解。Pax 3的异常过度O-GlcNAc化可能是导致高血糖相关神经管缺陷的原因。
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.
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影响因子：
2.7
作者：
Degenhardt KR;Milewski RC;Padmanabhan A;Miller M;Singh MK;Lang D;Engleka KA;Wu M;Li J;Zhou D;Antonucci N;Li L;Epstein JA
通讯作者：
Epstein JA
DOI：
10.1016/j.bbagrm.2014.04.023
发表时间：
2014-05
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Oraly Sanchez-Ferras;Guillaume Bernas;Emilie Laberge-Perrault;N. Pilon
通讯作者：
Oraly Sanchez-Ferras;Guillaume Bernas;Emilie Laberge-Perrault;N. Pilon
影响因子：
8.2
作者：
Pintaudi, Basilio;Lucisano, Giuseppe;Nicolucci, Antonio
通讯作者：
Nicolucci, Antonio
影响因子：
16.2
作者：
Jeremy S. Kaplan;Saba Iqbal;B. England;C. M. Zawacki;W. Herman
通讯作者：
Jeremy S. Kaplan;Saba Iqbal;B. England;C. M. Zawacki;W. Herman
影响因子：
--
作者：
Shant Kumar;M. Slevin;Patricia Kumar;Qiuyu Wang
通讯作者：
Shant Kumar;M. Slevin;Patricia Kumar;Qiuyu Wang