z-logo
Premium
Astrocytic insulin‐like growth factor‐1 prevents excitotoxic downregulation of adenosine deaminase acting on RNA in calcium dynamics
Author(s) -
Chen Wei,
He Bin,
Zheng Ping
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28184
Subject(s) - adar , microbiology and biotechnology , downregulation and upregulation , excitotoxicity , astrocyte , rna editing , biology , glutamate receptor , rna , adenosine deaminase , chemistry , biochemistry , adenosine , endocrinology , receptor , gene , central nervous system
Background A‐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. Method To 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. Results We 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. Conclusion Astrocytic IGF‐1 has a neuroprotective role in preventing excitotoxic downregulation of ADAR1 in mediating calcium dynamics via STAT2.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here