title: ErbB receptors and PKC regulate PC12 neuronal-like differentiation and sodium current elicitation.
abstract: Excitability, neurite outgrowth and their specification are very important features in the establishment of neuronal differentiation. We have studied a conditioned medium (CM) from sciatic nerve which is able to induce a neuronal-like differentiation of PC12 cells. Previously, we have demonstrated that supplementing this CM with a generic inhibitor (k252a), which mainly inhibits tropomyosin-related kinase receptors (Trk receptors) and protein kinase C (PKC), caused neurite elongation, sodium current induction and axon development. In the present work, we are showing that the enhancement of neurite length and induction of sodium currents induced by CM+k252a were prevented by ErbB receptor inhibition. Additionally, we demonstrated that specific inhibition of PKC produced a similar effect to that exerted by k252a in CM-treated cells, specifically by increasing the percentage of differentiated cells with long neurites and inducing sodium currents. Moreover, CM changed the mRNA levels for ErbB2 and ErbB3 increasing them 6- and 36-folds respectively compared to their control. The inclusion of k252a with CM changed the ErbB1, ErbB2 and ErbB3 mRNA proportions increasing those eight-, seven- and fivefolds respectively. From this point, it is clear that appropriate ErbB receptor levels and PKC inhibition are necessary to enhance the effect of the CM in inducing the neuronal-like differentiation of PC12 cells. In summary, we demonstrated the involvement of ErbB receptors in the regulation of neurite elongation and sodium current induction in PC12 cells and propose that these processes could be initiated by ErbB receptors followed by a fine regulation of PKC signaling. These findings might implicate a novel interplay between ErbB receptors and PKC in the regulation of these molecular mechanisms.
authors: Unidad de Neurociencias, Instituto de Estudios Avanzados (IDEA), Caracas 1015A, Venezuela.
authors: L
authors: L
authors: García
authors: C
authors: C
authors: Castillo
authors: J
authors: J
authors: Carballo
authors: Y
authors: Y
authors: Rodríguez
authors: P
authors: P
authors: Forsyth
authors: R
authors: R
authors: Medina
authors: J C
authors: JC
authors: Martínez
authors: M
authors: M
authors: Longart
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017077:Culture Media, Conditioned; D066246:ErbB Receptors; D011493:Protein Kinase C; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3