闡明腺核苷三磷酸(ATP)在星狀膠細胞與神經元互動的訊息途徑與調控機制

P2 Purinergic Receptors and Astrocyte-Neuron Interaction
Our research interest is to elucidate the molecular mechanisms of ATP-stimulated signal transduction pathways and physiological functions of astrocytes in the central nervous system. Although astrocytes do not have action potential but are able to transmit fast signaling via Ca2+ signaling. Using a clonal astrocytes cell lines, RBA-2, we demonstrated that these astrocytes possess several ATP P2 receptors and there are two large families of P2 receptors, the P2Y G-protein-coupled metabotropic receptors and P2X ionotropic receptors, P2X containing seven subtypes and P2Y containing at least 8 subtypes. We found that RBA-2 astrocytes possess at least three P2 receptors, P2Y1, P2X4 and P2X7 and activation of P2X7 receptor induced Ca2+ influx, stimulated GABA release and enhanced the expression of an anti-inflammatory cytokine TGF-beta 1. Currently, we are examining the signaling and functions of P2Y1 and P2X4 receptors using a single cell Ca2+ imaging system. We found that ATP induced a biphasic Ca2+ signaling through activation of P2Y1 receptor. We are now elucidation of the mechanisms involving in the activation and desensitization of P2Y1 receptors. Since P2 receptors are known to play an important role in neuron-astrocyte interaction, we also examine the roles of P2 receptor expression in neuronal cells.

• • Chen H. B., Sun S. H (2006) Oxidized ATP (oATP) Oxidized ATP decreases actin expression and intracellular superoxide concentrations in RBA-2 type 2 astrocytes independently of P2X7 receptor. Eur. J. Pharmacol. 550:1–7. (SCI)
  • Chen HB, Chan Y-T, Hung AC, Tsai Y-C and Sun SH (2006) Elucidation of ATP-stimulated stress protein expression of RBA-2 type-2 astrocytes: ATP potentiate HSP60 and Cu/Zn SOD expression and stimulates pI shift of peroxiredoxin II, J. Cell. Biochem. 97:314-326. (SCI)
  • Hung, A. C., Chu Y-J, Lin Y-H, Weng J-Y, Chen HB, Au Y-C and Sun SH (2005) Roles of protein kinase C in regulation of P2X7 receptor-mediated calcium signalling of cultured type-2 astrocyte cell line, RBA-2. Cellular Signalling, 17(11):1384-1396. (SCI)
  • Wang, C.-M., Chang, Y.-Y. and Sun, S. H. (2003) Activation of P2X7 purinoceptor stimulated TGF-b1 mRNA expression via PKC/MAPK pathway in the RBA-2 type-2 astrocytes. Cellular Signalling, 15, 1129-1137. (SCI)
  • Ju, Y. J., Wang, C.-M. Hung, A. C., Lo, J.-C. Lin, H.-J. and Sun, S. H. (2003) Endothelin-1 stimulated capacitative Ca2+ entry through ETA receptors of a rat brain-derived type-1 astrocyte cell line, IA-1g1 Cellular Signaling, 15, 197-207. (SCI)
  • Wang, C.-M., Chang, Y.-Y., Kuo, J.-S. and Sun, S. H. (2002) Activation of P2X7 receptors induced [3H]GABA release from RBA-2 type-2 astrocyte cell line through a Cl-/HCO3–dependent mechanism. Glia, 37, 8-18. (SCI)
  • Hung, A. C. and Sun, S. H. (2002) Characterization of the P2X7 receptor-mediated phosphatidylcholine-phospholipase D activities in a rat brain-derived type-2 astrocyte cell line, RBA-2: Involvement of PKC-dependent and PKC-independent pathways. Cellular Signalling, 14, 1-10. (SCI)
  • Elucidation of molecular mechanisms involving in P2Y1 and P2X4 mediated Ca2+ signaling and physiologicalfunctions of RBA-2 astrocytes.
  • Potential link between systemic inflammation and neuronal degeneration–the role of neuron-glia cross talk: Neuroimmune responses of astrocytes and their effects on neuronal functions.
  • Elucidation of molecular mechanisms of ATP and endothelin-1 stimulate signal transduction pathways and physiological function of astrocytes.
  • Elucidation of molecular mechanisms of P2X7 receptor-mediated signal transducntion pathways and physioilogical functions of RBA-2 astrocytes.
  • Adminiastration of Education.Human brain project, from gene to cognition: effect of stress on neural cells.