Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Adv Exp Med Biol. 2020;1202:35-65. doi: 10.1007/978-3-030-30651-9_3.
The chapter is focused on the mechanism of action of metabotropic P2Y nucleotide receptors: P2Y, P2Y, P2Y, P2Y and the ionotropic P2X receptor in glioma C6 cells. P2Y and P2Y both respond to ADP, but while P2Y links to PLC and elevates cytosolic Ca concentration, P2Y negatively couples to adenylate cyclase, maintaining cAMP at low level. In glioma C6, these two P2Y receptors modulate activities of ERK1/2 and PI3K/Akt signaling and the effects depend on physiological conditions of the cells. During prolonged serum deprivation, cell growth is arrested, the expression of the P2Y receptor strongly decreases and P2Y becomes a major player responsible for ADP-evoked signal transduction. The P2Y receptor activates ERK1/2 kinase phosphorylation (a known cell proliferation regulator) and stimulates Akt activity, contributing to glioma invasiveness. In contrast, P2Y has an inhibitory effect on Akt pathway signaling. Furthermore, the P2X receptor, often responsible for apoptotic fate, is not involved in Caelevation in C6 cells. The shift in nucleotide receptor expression from P2Y to P2Y during serum withdrawal, the cross talk between both receptors and the lack of P2X activity shows the precise self-regulating mechanism, enhancing survival and preserving the neoplastic features of C6 cells.
这一章专注于代谢型 P2Y 核苷酸受体的作用机制：P2Y、P2Y、P2Y、P2Y 和离子型 P2X 受体在神经胶质瘤 C6 细胞中的作用。P2Y 和 P2Y 都对 ADP 有反应，但 P2Y 与 PLC 相连并升高细胞浆 Ca 浓度，而 P2Y 则与腺苷酸环化酶负耦联，使 cAMP 保持在低水平。在神经胶质瘤 C6 中，这两种 P2Y 受体调节 ERK1/2 和 PI3K/Akt 信号通路的活性，其效应取决于细胞的生理状况。在长时间血清剥夺时，细胞生长被抑制，P2Y 受体的表达强烈下降，P2Y 成为负责 ADP 诱发信号转导的主要角色。P2Y 受体激活 ERK1/2 激酶磷酸化（已知的细胞增殖调节剂），并刺激 Akt 活性，有助于神经胶质瘤的侵袭性。相反，P2Y 对 Akt 通路信号具有抑制作用。此外，通常负责细胞凋亡命运的 P2X 受体，不参与 C6 细胞中的 Ca 升高。在血清剥夺时，核苷酸受体表达从 P2Y 向 P2Y 的转变，两种受体之间的串扰以及缺乏 P2X 活性，显示出精确的自我调节机制，增强了 C6 细胞的生存能力并保持了其肿瘤特征。
