PROTEIN KINASE A AND Epac ACTIVATION BY cAMP REGULATES THE EXPRESSION OF GLIAL FIBRILLARY ACIDIC PROTEIN IN GLIAL CELLS

Naotoshi Sugimoto, Shinji Miwa, Hiroyuki Nakamura, Hiroyuki Tsuchiya, Akihiro Yachie

Abstract


Cyclic adenosine monophosphate (cAMP) controls differentiation in several types of cells during brain development. However, the molecular mechanism of cAMP-controlled differentiation is not fully understood. We investigated the role of protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac) on cAMP-induced glial fibrillary acidic protein (GFAP), an astrocyte marker, in cultured glial cells. B92 glial cells were treated with cAMP-elevating drugs, an activator of adenylate cyclase, phosphodiesterase inhibitor and a ß adrenal receptor agonist. These cAMP-elevating agents induced dramatic morphological changes and expression of GFAP. A cAMP analog, 8-Br-cAMP, which activates Epac as well as PKA, induced GFAP expression and morphological changes, while another cAMP analog, 8-CPT-cAMP, which activates Epac with greater efficacy when compared to PKA, induced GFAP expression but very weak morphological changes. Most importantly, the treatment with a PKA inhibitor partially reduced cAMP-induced GFAP expression. Taken together, these results indicate that cAMP-elevating drugs lead to the induction of GFAP via PKA and/or Epac activation in B92 glial cells.

DOI: 10.2298/ABS160112067S

Key words: adenylate cyclase; Epac; GFAP; phosphodiesterase; PKA

Received: January 12, 2016; Revised: February 1, 2016; Accepted: February 2, 2016; Published online: August 3, 2016

How to cite this article: Sugimoto N, Miwa S, Nakamura H, Tsuchiya H, Yachie A. Protein kinase A and Epac activation by cAMP regulates the expression of glial fibrillary acidic protein in glial cells. Arch Biol Sci. 2016;68(4):795-801.


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