Astrocytic insulin-like growth factor-1 prevents excitotoxic downregulation of adenosine deaminase acting on RNA in calcium dynamics

作者：Chen, Wei; He, Bin; Zheng, Ping^*

来源：Journal of Cellular Biochemistry, 2019, 120(6): 9097-9103.

DOI：10.1002/jcb.28184

• adenosine to inosine acting on RNA enzyme 1 (ADAR1)
• calcium overload
• excitotoxicity
• insulin-like growth factor (IGF)-1

BackgroundA-to-I RNA editing catalyzed by the adenosine deaminase acting on RNA (ADAR) 1 represents an RNA-based recoding mechanism implicated in a variety of cellular processes like intracellular homeostasis. Previous studies have demonstrated that the expression of ADAR1 is increased in glioma, and ADAR1 short hairpin RNA affects regulated cellular exocytosis. This indicates that ADAR1 might be involved in cellular proliferation and/or apoptosis.
MethodTo investigate the molecular mechanism by which ADAR1 is activity dependent, we applied the primary neuron culture and coculture with astrocytes and the RNA chipset to explore the underlying mechanism.
ResultsWe found that in primary cultured neurons, the excitotoxicity induced by kainic acid (KA) increased the cellular calcium concentration determined by flow cytometry, and cocultured astrocyte could decrease the calcium concentration in KA-treated neurons. In addition, we applied RNA chipset and found KA decreased the ADAR1 and signal transducer and activator of transcription 2 (STAT2) expression and cocultured astrocytes could increase the insulin-like growth factor (IGF)-1 expression and reverse the reduced ADAR1 and STAT2. This effect can be abolished by the astrocytic IGF-1 with AG1024.
ConclusionAstrocytic IGF-1 has a neuroprotective role in preventing excitotoxic downregulation of ADAR1 in mediating calcium dynamics via STAT2.

• 出版日期2019-6
• 单位上海大学; 上海市浦东新区人民医院