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MeSH Review

PC12 Cells

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Disease relevance of PC12 Cells


Psychiatry related information on PC12 Cells

  • Recent studies have identified the Alzheimer's disease amyloid beta/A4 protein precursor (APP) as a trophic and/or tropic protein on several types of cells, including fibroblasts, primary culture neurons, PC12 cells, and B103 neuron-like cells [6].
  • This investigation examined if lithium, the primary therapeutic treatment for bipolar affective disorder, modulated the levels of selected signal transduction proteins in PC12 cells [7].
  • Our findings suggest that sigma2 receptors are coupled to the DAT via a Ca2+/calmodulin-dependent protein kinase II transduction system in PC12 cells, and that sigma2 receptor antagonists might be useful in the treatment of drug abuse by blocking elevation of DA levels via reversal of the DAT [8].
  • Interestingly, however, in the nerve treated with tumor necrosis factor-alpha (but not in the nerve treated with colony stimulating factor-1) this increase was accompanied by an increased permissiveness of the nerve to neuronal adhesion, which we examined in vitro using longitudinal sections of the nerve on which PC12 cells were seeded [9].

High impact information on PC12 Cells


Chemical compound and disease context of PC12 Cells


Biological context of PC12 Cells

  • Treatment of PC12 cells with nerve growth factor (NGF) induces a rapid increase in tyrosine phosphorylation of multiple cellular proteins [20].
  • We report that in PC12 cells, expression of a dominant inhibitory mutant of ras, c-Ha-ras(Asn-17), antagonizes growth factor- and phorbol ester-induced activation of the erk-encoded family of MAP kinases, the 85-92 kd RSKs, and the kinase(s) responsible for hyperphosphorylation of the proto-oncogene product Raf-1 [21].
  • Transfection of PC12 cells with the amino-terminal domains of Rim greatly enhances regulated exocytosis in a Rab3-dependent manner [22].
  • In vivo, dominant negative Ras mutant N17 inhibits growth factor induced production of 3' phosphorylated phosphoinositides in PC12 cells, and transfection of Ras, but not Raf, into COS cells results in a large elevation in the level of these lipids [23].
  • Similar cAMP induction was obtained with the transfected chromogranin A promoter in PC12 cells, and abolition of the CRE site (by deletion or point mutation) eliminated the induction [24].

Anatomical context of PC12 Cells


Associations of PC12 Cells with chemical compounds

  • PC12 cells mutagenized with ethyl methanesulfonate were cultured in the presence of NGF, causing normal cells to cease proliferation and allowing the isolation of cell clones which do not show growth inhibition by NGF [30].
  • We have recently shown that highly purified BWSTx stimulates secretion from PC12 cells of previously taken up radioactive dopamine (DA) and noradrenaline (NA) (ref. 14 and manuscript in preparation) [31].
  • Functional acetylcholine receptor in PC12 cells reacts with a monoclonal antibody to brain nicotinic receptors [32].
  • We also show that at low concentrations FK506 and cyclosporin A enhance the phosphorylation of endogenous protein substrates in brain tissue and in intact PC12 cells, indicating that these drugs may inhibit phosphatase activity by interacting with the immunophilin-calcineurin complexes [33].
  • A functional consequence of this interaction was revealed by measuring a PAF-elicited, Ca2+-dependent secretion of adenosine triphosphate from PC12 cells [34].

Gene context of PC12 Cells


Analytical, diagnostic and therapeutic context of PC12 Cells

  • In addition, PC12 cells expressing Wnt-1 (PC12/Wnt-1) fail to extend neurites after treatment with NGF, despite the presence and activation of high affinity NGF receptors encoded by the trk gene and the induction of early response genes [40].
  • Antibodies directed against recombinant VGF8a-beta-galactosidase fusion proteins were used for immunofluorescent staining of the protein in PC12 cells as well as for its localization, by Western blot analysis, in subfractions of cell homogenates [41].
  • Immunoprecipitation from particulate and cytosolic fractions of PC12 cells confirmed that compactin blocks p21ras membrane association: p21ras is confined to the cytosol fraction [42].
  • To study microtubule (MT) dynamics in nerve cells, we microinjected biotin-labeled tubulin into the cell body of chemically fused and differentiated PC12 cells and performed the immunofluorescence or immunogold procedure using an anti-biotin antibody followed by secondary antibodies coupled to fluorescent dye or colloidal gold [43].
  • Coculture of these cells with C2 cells results in the clustering of N-CAM at heterologous contacts between C2 cells and NRK, CHO, or PC12 cells, but not between C2 cells and L929 cells [44].


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  2. Rac regulates phosphorylation of the myosin-II heavy chain, actinomyosin disassembly and cell spreading. van Leeuwen, F.N., van Delft, S., Kain, H.E., van der Kammen, R.A., Collard, J.G. Nat. Cell Biol. (1999) [Pubmed]
  3. The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC12 cells. Richter-Landsberg, C., Jastorff, B. J. Cell Biol. (1986) [Pubmed]
  4. Differential transactivation of sphingosine-1-phosphate receptors modulates NGF-induced neurite extension. Toman, R.E., Payne, S.G., Watterson, K.R., Maceyka, M., Lee, N.H., Milstien, S., Bigbee, J.W., Spiegel, S. J. Cell Biol. (2004) [Pubmed]
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  6. Secreted form of amyloid beta/A4 protein precursor (APP) binds to two distinct APP binding sites on rat B103 neuron-like cells through two different domains, but only one site is involved in neuritotropic activity. Ninomiya, H., Roch, J.M., Jin, L.W., Saitoh, T. J. Neurochem. (1994) [Pubmed]
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  8. Modulation of amphetamine-stimulated [3H]dopamine release from rat pheochromocytoma (PC12) cells by sigma type 2 receptors. Weatherspoon, J.K., Werling, L.L. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  9. Cytokines modulate the inflammatory response and change permissiveness to neuronal adhesion in injured mammalian central nervous system. Lotan, M., Solomon, A., Ben-Bassat, S., Schwartz, M. Exp. Neurol. (1994) [Pubmed]
  10. SNARE complex formation is triggered by Ca2+ and drives membrane fusion. Chen, Y.A., Scales, S.J., Patel, S.M., Doung, Y.C., Scheller, R.H. Cell (1999) [Pubmed]
  11. cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway. Vossler, M.R., Yao, H., York, R.D., Pan, M.G., Rim, C.S., Stork, P.J. Cell (1997) [Pubmed]
  12. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Marshall, C.J. Cell (1995) [Pubmed]
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  15. Two peptides derived from the nerve growth factor precursor are biologically active. Dicou, E., Pflug, B., Magazin, M., Lehy, T., Djakiew, D., Ferrara, P., Nerrière, V., Harvie, D. J. Cell Biol. (1997) [Pubmed]
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  17. Affinity labeling and partial purification of nerve growth factor receptors from rat pheochromocytoma and human melanoma cells. Grob, P.M., Berlot, C.H., Bothwell, M.A. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  18. D2-Like dopamine autoreceptor activation reduces quantal size in PC12 cells. Pothos, E.N., Przedborski, S., Davila, V., Schmitz, Y., Sulzer, D. J. Neurosci. (1998) [Pubmed]
  19. Regulation of bradykinin- and ATP-activated Ca(2+)-permeable channels in rat pheochromocytoma (PC12) cells. Neuhaus, R., Reber, B.F., Reuter, H. J. Neurosci. (1991) [Pubmed]
  20. Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases. Thomas, S.M., DeMarco, M., D'Arcangelo, G., Halegoua, S., Brugge, J.S. Cell (1992) [Pubmed]
  21. ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK. Wood, K.W., Sarnecki, C., Roberts, T.M., Blenis, J. Cell (1992) [Pubmed]
  22. Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion. Wang, Y., Okamoto, M., Schmitz, F., Hofmann, K., Südhof, T.C. Nature (1997) [Pubmed]
  23. Phosphatidylinositol-3-OH kinase as a direct target of Ras. Rodriguez-Viciana, P., Warne, P.H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M.J., Waterfield, M.D., Downward, J. Nature (1994) [Pubmed]
  24. A functional cyclic AMP response element plays a crucial role in neuroendocrine cell type-specific expression of the secretory granule protein chromogranin A. Wu, H., Mahata, S.K., Mahata, M., Webster, N.J., Parmer, R.J., O'Connor, D.T. J. Clin. Invest. (1995) [Pubmed]
  25. Cloning of complementary DNA for GAP-43, a neuronal growth-related protein. Karns, L.R., Ng, S.C., Freeman, J.A., Fishman, M.C. Science (1987) [Pubmed]
  26. Synaptophysin is sorted from endocytotic markers in neuroendocrine PC12 cells but not transfected fibroblasts. Linstedt, A.D., Kelly, R.B. Neuron (1991) [Pubmed]
  27. Processing of chromogranin A by plasmin provides a novel mechanism for regulating catecholamine secretion. Parmer, R.J., Mahata, M., Gong, Y., Mahata, S.K., Jiang, Q., O'Connor, D.T., Xi, X.P., Miles, L.A. J. Clin. Invest. (2000) [Pubmed]
  28. Synaptotagmin IV is necessary for the maturation of secretory granules in PC12 cells. Ahras, M., Otto, G.P., Tooze, S.A. J. Cell Biol. (2006) [Pubmed]
  29. ADP ribosylation factor 1 is required for synaptic vesicle budding in PC12 cells. Faúndez, V., Horng, J.T., Kelly, R.B. J. Cell Biol. (1997) [Pubmed]
  30. Clonal variants of PC12 pheochromocytoma cells with altered response to nerve growth factor. Bothwell, M.A., Schechter, A.L., Vaughn, K.M. Cell (1980) [Pubmed]
  31. Black widow spider toxin-induced calcium fluxes and transmitter release in a neurosecretory cell line. Grasso, A., Alemà, S., Rufini, S., Senni, M.I. Nature (1980) [Pubmed]
  32. Functional acetylcholine receptor in PC12 cells reacts with a monoclonal antibody to brain nicotinic receptors. Whiting, P.J., Schoepfer, R., Swanson, L.W., Simmons, D.M., Lindstrom, J.M. Nature (1987) [Pubmed]
  33. High brain densities of the immunophilin FKBP colocalized with calcineurin. Steiner, J.P., Dawson, T.M., Fotuhi, M., Glatt, C.E., Snowman, A.M., Cohen, N., Snyder, S.H. Nature (1992) [Pubmed]
  34. Neuroregulatory and neuropathological actions of the ether-phospholipid platelet-activating factor. Kornecki, E., Ehrlich, Y.H. Science (1988) [Pubmed]
  35. Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras. Rosen, L.B., Ginty, D.D., Weber, M.J., Greenberg, M.E. Neuron (1994) [Pubmed]
  36. The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC12 cells. Tsoulfas, P., Soppet, D., Escandon, E., Tessarollo, L., Mendoza-Ramirez, J.L., Rosenthal, A., Nikolics, K., Parada, L.F. Neuron (1993) [Pubmed]
  37. Identification and characterization of novel substrates of Trk receptors in developing neurons. Qian, X., Riccio, A., Zhang, Y., Ginty, D.D. Neuron (1998) [Pubmed]
  38. Small GTPase Rin induces neurite outgrowth through Rac/Cdc42 and calmodulin in PC12 cells. Hoshino, M., Nakamura, S. J. Cell Biol. (2003) [Pubmed]
  39. Cellubrevin and synaptobrevins: similar subcellular localization and biochemical properties in PC12 cells. Chilcote, T.J., Galli, T., Mundigl, O., Edelmann, L., McPherson, P.S., Takei, K., De Camilli, P. J. Cell Biol. (1995) [Pubmed]
  40. The Wnt-1 proto-oncogene induces changes in morphology, gene expression, and growth factor responsiveness in PC12 cells. Shackleford, G.M., Willert, K., Wang, J., Varmus, H.E. Neuron (1993) [Pubmed]
  41. A protein induced by NGF in PC12 cells is stored in secretory vesicles and released through the regulated pathway. Possenti, R., Eldridge, J.D., Paterson, B.M., Grasso, A., Levi, A. EMBO J. (1989) [Pubmed]
  42. ras isoprenylation is required for ras-induced but not for NGF-induced neuronal differentiation of PC12 cells. Qiu, M.S., Pitts, A.F., Winters, T.R., Green, S.H. J. Cell Biol. (1991) [Pubmed]
  43. Microtubule dynamics in nerve cells: analysis using microinjection of biotinylated tubulin into PC12 cells. Okabe, S., Hirokawa, N. J. Cell Biol. (1988) [Pubmed]
  44. Clusters of neural cell adhesion molecule at sites of cell-cell contact. Bloch, R.J. J. Cell Biol. (1992) [Pubmed]
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