Premium
Activation of adenosine A 1 receptor–induced neural stem cell proliferation via MEK/ERK and Akt signaling pathways
Author(s) -
Migita Hideyuki,
Kominami Katsuya,
Higashida Mami,
Maruyama Rumi,
Tuchida Nobuko,
McDonald Fiona,
Shimada Fumiki,
Sakurada Kazuhiro
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21742
Subject(s) - protein kinase b , adenosine , mapk/erk pathway , neural stem cell , microbiology and biotechnology , adenosine kinase , adenosine receptor , signal transduction , biology , purinergic signalling , kinase , adenosine a1 receptor , phosphorylation , chemistry , agonist , receptor , stem cell , endocrinology , biochemistry , adenosine deaminase
Adenosine, a modulator of neuronal function in the mammalian central nervous system, exerts a neuroprotective effect via the adenosine A 1 receptor; however, its effect on neural stem cells (NSCs) remains unclear. Because adenosine is released in response to pathological conditions and NSCs play a key role in neuroregeneration, we tested the hypothesis that adenosine is capable of stimulating NSC proliferation. We demonstrated that NSCs dominantly express adenosine A 1 and A 2B receptors. Adenosine and the adenosine A 1 receptor agonist cyclopentyladenosine (CPA) increased proliferation of NSCs, and this CPA‐induced cell proliferation was attenuated by the A 1 antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPA). CPA also induced phosphorylation of extracellular signal–regulated kinase (ERK), mitogen‐activated protein kinase/ERK kinase (MEK), and Akt, and their phosphorylation was inhibited by DPCPA. In addition, CPA‐induced cell proliferation was inhibited by MEK and Akt inhibitors. These results suggest that activation of adenosine A 1 receptor–stimulated proliferation of NSCs occurs via MEK/ERK and Akt signaling pathways. © 2008 Wiley‐Liss, Inc.