Regulatory function of praja ring finger ubiquitin ligase 2 mediated by the P2rx3/P2rx7 axis in mouse hippocampal neuronal cells

	Regulatory function of praja ring finger ubiquitin ligase 2 mediated by the P2rx3/P2rx7 axis in mouse hippocampal neuronal cells
	Gong, Mengting; Ye, Shoudong; Li, Wen-Xing; Zhang, Jian; Liu, Yanjun; Zhu, Jie; Lv, Wenwen; Zhang, Hui; Wang, Jing; Lu, Aiping; He, Kan
	2020
发表期刊	AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
ISSN	0363-6143
卷号	318 期号:6 页码:C1123-C1135
摘要	Praja2 (Pja2), a member of the growing family of mammalian RING E3 ubiquitin ligases, is reportedly involved in not only several types of cancer but also neurological diseases and disorders, but the genetic mechanism underlying the regulation of Pja2 in the nervous system remains unclear. To study the cellular and molecular functions of Pja2 in mouse hippocampal neuronal cells (MHNCs), we used gain- and loss-of-function manipulations of Pja2 in HT-22 cells and tested their regulatory effects on three Alzheimer's disease (AD) genes and cell proliferation. The results revealed that the expression of AD markers, including amyloid beta precursor protein (App), microtubule-associated protein tau (Mapt), and gamma-secretase activating protein (Gsap), could be inhibited by Pja2 overexpression and activated by Pja2 knockdown. In addition, HT-22 cell proliferation was enhanced by Pja2 upregulation and suppressed by its downregulation. We also evaluated and quantified the targets that responded to the enforced expression of Pja2 by RNA-Seq, and the results showed that purinergic receptor P2X, ligand-gated ion channel 3 and 7 (P2rx3 and P2rx7), which show different expression patterns in the critical calcium signaling pathway, mediated the regulatory effect of Pja2 in HT-22 cells. Functional studies indicated that Pja2 regulated HT-22 cells development and AD marker genes by inhibiting P2rx3 but promoting P2rx7, a gene downstream of P2rx3. In conclusion, our results provide new insights into the regulatory function of the Pja2 gene in MHNCs and thus underscore the potential relevance of this molecule to the pathophysiology of AD.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/12946
专题	科研部门_动物模型与人类重大疾病机理重点实验室
推荐引用方式 GB/T 7714	Gong, Mengting,Ye, Shoudong,Li, Wen-Xing,et al. Regulatory function of praja ring finger ubiquitin ligase 2 mediated by the P2rx3/P2rx7 axis in mouse hippocampal neuronal cells[J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,2020,318(6):C1123-C1135.
APA	Gong, Mengting.,Ye, Shoudong.,Li, Wen-Xing.,Zhang, Jian.,Liu, Yanjun.,...&He, Kan.(2020).Regulatory function of praja ring finger ubiquitin ligase 2 mediated by the P2rx3/P2rx7 axis in mouse hippocampal neuronal cells.AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,318(6),C1123-C1135.
MLA	Gong, Mengting,et al."Regulatory function of praja ring finger ubiquitin ligase 2 mediated by the P2rx3/P2rx7 axis in mouse hippocampal neuronal cells".AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 318.6(2020):C1123-C1135.

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