Disease relevance of PC12 Cells

• Here we present data on the effect of infection of PC12 cells with retroviruses carrying the src oncogene of Rous sarcoma virus [1].
• Stimulation of PC12 cells or N1E-115 neuroblastoma cells with bradykinin induces phosphorylation of threonine residues in the myosin-II heavy chain; this phosphorylation is Ca2+ dependent and regulated by Rac [2].
• Nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells has been described to be synergistically potentiated by the simultaneous addition of dibutyryl cAMP [3].
• In this paper, we report that in PC12 cells and dorsal root ganglion neurons, NGF translocates SphK1 to the plasma membrane and differentially activates the S1P receptors S1P1 and S1P2 in a SphK1-dependent manner, as determined with specific inhibitors and small interfering RNA targeted to SphK1 [4].
• To investigate whether this sorting was due to coaggregation of the deletion mutant with endogenous granins, we expressed human CgB using recombinant vaccinia viruses, under conditions in which the synthesis of endogenous granins in the infected PC12 cells was shut off [5].

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

• Botulinum neurotoxin E inhibition of norepinephrine release in permeabilized PC12 cells can be rescued by adding a 65 aa C-terminal fragment of SNAP-25 (S25-C) [10].
• We show here that cAMP can activate the transcription factor Elk-1 and induce neuronal differentiation of PC12 cells via its activation of the MAP kinase cascade [11].
• Experiments with PC12 cells also suggest that the duration of ERK activation is critical for cell signaling decisions [12].
• Microinjection studies suggest that the nervous system-specific syntaxin 1A is important for calcium-regulated secretion from neuro-endocrine PC12 cells [13].
• Microinjection of monoclonal and polyclonal antibodies raised against synaptotagmin (p65), but not the other vesicle proteins, decreases K+/Ca(2+)-mediated dopamine beta-hydroxylase surface staining, a measure of regulated secretion in PC12 cells [14].

Chemical compound and disease context of PC12 Cells

• Furthermore, both propeptides induced rapid tyrosine phosphorylation of the Trk protein in both prostatic adenocarcinoma cells and PC12 cells, thus implicating trk in their mechanism of action [15].
• Variant rat pheochromocytoma (PC12) cells which fail to respond to nerve growth factor (NGF) (PC12nnr5) (Green, S. H., R. E. Rydel, J. L. Connoly, and L. A. Greene. 1986. J. Cell Biol. 102:830-843) bind NGF at both high and low affinity sites [16].
• Either ethyldimethylisopropyl-aminocarbodiimide or hydroxysuccinimidyl-p-azidobenzoate causes highly specific crosslinking of 125I-NGF to a similar receptor species on rat pheochromocytoma PC12 cells and on human melanoma A875 cells [17].
• To directly observe the effects of D2 autoreceptors on exocytic neurotransmitter release, we measured quantal release of dopamine from pheochromocytoma PC12 cells that express D2 and D4 autoreceptors [18].
• Regulation of bradykinin- and ATP-activated Ca(2+)-permeable channels in rat pheochromocytoma (PC12) cells [19].

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

• Nerve growth factor or adenosine 3',5'-monophosphate induction of neurites from PC12 cells is accompanied by increased GAP-43 expression [25].
• Synaptophysin is sorted from endocytotic markers in neuroendocrine PC12 cells but not transfected fibroblasts [26].
• Peptides generated by plasmin-mediated cleavage of CgA significantly inhibited nicotinic cholinergic stimulation of catecholamine release from PC12 cells and primary bovine adrenal chromaffin cells [27].
• Synaptotagmin IV is necessary for the maturation of secretory granules in PC12 cells [28].
• Thus, the generation of SVs from PC12 cell membranes requires ARF and uses its GTPase activity, probably to regulate coating phenomena [29].

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

• In PC12 cells, membrane depolarization leading to calcium influx through L-type calcium channels activates the dual specificity MAPK kinase MEK1, which phosphorylates and activates MAPK [35].
• The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC12 cells [36].
• Moreover, rAPS and SH2-B bind to Grb2, and both are sufficient to mediate NGF induction of Ras, MAP kinase (MAPK), and morphological differentiation of PC12 cells [37].
• Small GTPase Rin induces neurite outgrowth through Rac/Cdc42 and calmodulin in PC12 cells [38].
• In PC12 cells, cellubrevin has a distribution very similar to that of synaptobrevin 1 and 2 [39].

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].

References