Tsang Hing-Wai, Bhatia Inderjeet, Chan Koon-Wing, Chan Godfrey Chi-Fung, Ip Patrick, Cheung Pik-To
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;
Room 123, 1/F, New Clinical Building, Queen Mary Hospital, Hong Kong, China.
NeuroSci. 2022 Jan 1;3(1):41-51. doi: 10.3390/neurosci3010003. eCollection 2022 Mar.
Transmembrane 29 () gene with unknown function is a gene located on the X chromosome of the mouse genome. The gene showed differential expression in the Vannucci neonatal hypoxic-ischemic mouse brain model. We found the gene expresses with different molecular forms, including a group of long non-coding RNA forming a family of transcripts. It was predominantly expressed in the testes, brain, and kidney of mouse. In vitro identification and functional characterization were carried out in Neuro2a cells. Using fluorescence microscopy, protein was found to be constitutively expressed in mouse cell lines of different origins. Oxygen glucose deprivation (OGD) induced apoptotic cell death in Neuro2a cells and was confirmed by activations of caspase 3. protein was found to be associated with cell death especially at the time points of caspase 3 activations. A similar response was obtained in glucose deprivation (GD) cultures suggesting response to a common mechanism induced by OGD and GD. Downregulation of was induced by OGD and GD, further validating its response to hypoxia-ischemia (HI) insults. Our findings contributed to further understanding of molecular events after hypoxic-ischemic insults and opens new avenues for developing protective and therapeutic strategies for hypoxic-ischemic encephalopathy or even pathological programmed cell death.
功能未知的跨膜29（）基因是位于小鼠基因组X染色体上的一个基因。该基因在Vannucci新生儿缺氧缺血性小鼠脑模型中表现出差异表达。我们发现该基因以不同的分子形式表达，包括一组形成转录本家族的长链非编码RNA。它主要在小鼠的睾丸、脑和肾中表达。在Neuro2a细胞中进行了体外鉴定和功能表征。使用荧光显微镜，发现该蛋白在不同来源的小鼠细胞系中组成性表达。氧糖剥夺（OGD）诱导Neuro2a细胞凋亡性细胞死亡，并通过半胱天冬酶3的激活得到证实。发现该蛋白与细胞死亡有关，尤其是在半胱天冬酶3激活的时间点。在葡萄糖剥夺（GD）培养物中获得了类似的反应，表明对OGD和GD诱导的共同机制有反应。OGD和GD诱导该蛋白表达下调，进一步验证了其对缺氧缺血（HI）损伤的反应。我们的发现有助于进一步了解缺氧缺血性损伤后的分子事件，并为开发针对缺氧缺血性脑病甚至病理性程序性细胞死亡的保护和治疗策略开辟了新途径。
