Departments of Surgery (Neurosurgery, Neuroscience and Neurobiology), Hamilton NeuroRestorative Group (NRG), McMaster University, Health Sciences Centre, Hamilton, ON, Canada.
J Biol Regul Homeost Agents. 2013 Jul-Sep;27(3):673-80.
In previous studies, we have found that extracellular guanosine can stimulate endogenous progenitor/stem cell proliferation in the spinal cord following chronic injury and in the subventricular zone of the brains of rats afflicted with Parkinson's Disease. In this study, using neural stem cells isolated from one-day old rats, we found that guanosine could stimulate neural stem cell proliferation, and that the proliferation was not due to the guanosine metabolism mechanism since guanine, which is interconverted by an ecto-purine nucleoside phosphorylase from guanosine, has no stimulating effect on the proliferation of neural stem cells. We determined that second messenger cAMP was involved in the pathway as results showed that 100 microM guanosine stimulated cAMP accumulation. Using western blot analysis, we found that 100 microM guanosine can activate the phosphorylation of CREB without changing the total amount of CREB. In conclusion, guanosine can stimulate neural stem cell proliferation, and the cAMP-CREB pathway is involved in this biological effect.
在之前的研究中，我们发现细胞外鸟苷可以刺激慢性损伤后脊髓内的内源性祖细胞/干细胞增殖，以及帕金森病大鼠脑室下区的祖细胞/干细胞增殖。在这项研究中，我们使用从 1 天大的大鼠中分离的神经干细胞，发现鸟苷可以刺激神经干细胞增殖，并且这种增殖不是由于鸟苷代谢机制引起的，因为鸟嘌呤可以由外切嘌呤核苷磷酸化酶从鸟苷互变，但对神经干细胞的增殖没有刺激作用。我们确定第二信使 cAMP 参与了这一途径，因为结果表明 100μM 鸟苷可以刺激 cAMP 积累。通过 Western blot 分析，我们发现 100μM 鸟苷可以激活 CREB 的磷酸化，而不改变 CREB 的总量。总之，鸟苷可以刺激神经干细胞增殖，cAMP-CREB 途径参与了这一生物学效应。
