Activation of adenosine A1 receptor-induced neural stem cell proliferation via MEK/ERK and Akt signaling pathways.
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.
Migita
Hideyuki
H
Department of Stem Cell-Based Drug Discovery, Research Center Kobe, Bayer Yakuhin Ltd., Kobe, Japan.
Kominami
Katsuya
K
Higashida
Mami
M
Maruyama
Rumi
R
Tuchida
Nobuko
N
McDonald
Fiona
F
Shimada
Fumiki
F
Sakurada
Kazuhiro
K
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D043682:Receptor, Adenosine A1; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases