Lv Jie, Shao YinLin, Gao Yuan
Putuo District People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Physiatry Department, Putuo District People's Hospital, Tongji University, Shanghai 200061, China.
Brain Res. 2018 May 1;1686:65-71. doi: 10.1016/j.brainres.2018.02.028. Epub 2018 Feb 21.
Neural progenitor cells (NPCs) play a key role not only in the maintenance of the adult central nervous system (CNS) but also in the ability to recover from injury and disease. In this study, we established a 96-well-based screening system to screen small molecules modulating the proliferation of NPCs. A compound library composed of 1280 compounds was screened. We found that the A adenosine receptor agonist cyclopentyladenosine (CPA) and the A adenosine receptor agonist CGS-21680 increased proliferation of NPCs. The A adenosine receptor agonist-induced cell proliferation was attenuated by A adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPA). Accordingly, the A adenosine receptor agonist-induced cell proliferation was attenuated by A adenosine receptor antagonist SCH-58261. Further study indicated that CPA and CGS-21680 treatment induced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, and CPA-induced or CGS-21680-induced cell proliferation was inhibited by ERK and Akt inhibitors. These results suggested that the activation of A and A adenosine receptor stimulated the proliferation of NPCs via the ERK and Akt signaling pathways.
神经祖细胞（NPCs）不仅在维持成体中枢神经系统（CNS）中发挥关键作用，而且在从损伤和疾病中恢复的能力方面也起着关键作用。在本研究中，我们建立了一个基于96孔板的筛选系统，以筛选调节NPCs增殖的小分子。对一个由1280种化合物组成的化合物库进行了筛选。我们发现A1腺苷受体激动剂环戊腺苷（CPA）和A2A腺苷受体激动剂CGS-21680可增加NPCs的增殖。A1腺苷受体激动剂诱导的细胞增殖被A1腺苷受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPA）减弱。相应地，A2A腺苷受体激动剂诱导的细胞增殖被A2A腺苷受体拮抗剂SCH-58261减弱。进一步的研究表明，CPA和CGS-21680处理可诱导细胞外信号调节激酶（ERK）和Akt的磷酸化，并且ERK和Akt抑制剂可抑制CPA诱导或CGS-21680诱导的细胞增殖。这些结果表明，A1和A2A腺苷受体的激活通过ERK和Akt信号通路刺激了NPCs的增殖。
