Zhang Li, Dong Yanting, Wang Wenzhuo, Zhao Taoran, Huang Tingjuan, Khan Ajab, Wang Lei, Liu Zhizhen, Xie Jun, Niu Bo
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China.
Department of Respiratory and Critical Care Medicine, Second Hospital of Shanxi Medical University, Taiyuan, China.
Front Neurol. 2020 Apr 7;11:242. doi: 10.3389/fneur.2020.00242. eCollection 2020.
Abnormal development of central nervous system (CNS) caused by neural tube defects (NTDs) is not only remained the major contributor in the prevalence of stillbirths and neonatal deaths, but also represents a significant cause of lifelong physical disability in the surviving infants. Ethionine is a non-proteinogenic amino acid and antagonist of methionine. Methionine cycle is essential for the elimination of reactive oxygen species (ROS), while lysosomes are involved in the initiation of autophagy. However, its role in ethionine-induced cell death in neural tube defects, still need to be explored. In this study, we investigated the effect of ethionine on NTDs as well as the underlying mechanism involved in this process. Following the establishment of NTDs model using ethionine-induced C57BL/6 mice, ethionine was intraperitoneally injected at a dose of 500 mg/kg in E7.5. Our study revealed that ethionine has induced mitochondrial apoptosis in NTDs by reducing mitochondrial autophagy both and . These results provided a possible molecular mechanism for redox regulation of autophagic process.
神经管缺陷（NTDs）导致的中枢神经系统（CNS）异常发育不仅仍是死产和新生儿死亡流行率的主要因素，也是存活婴儿终身身体残疾的重要原因。乙硫氨酸是一种非蛋白质氨基酸和蛋氨酸拮抗剂。蛋氨酸循环对于消除活性氧（ROS）至关重要，而溶酶体参与自噬的启动。然而，其在神经管缺陷中乙硫氨酸诱导的细胞死亡中的作用仍有待探索。在本研究中，我们研究了乙硫氨酸对神经管缺陷的影响以及该过程中涉及的潜在机制。在用乙硫氨酸诱导C57BL / 6小鼠建立神经管缺陷模型后，在E7.5以500 mg / kg的剂量腹腔注射乙硫氨酸。我们的研究表明，乙硫氨酸通过减少线粒体自噬在神经管缺陷中诱导了线粒体凋亡。这些结果为自噬过程的氧化还原调节提供了一种可能的分子机制。
