PMA decreases the proliferation of retinal cells in vitro: the involvement of acetylcholine and BDNF.
Protein kinase C (PKC) is involved in several cell events including proliferation, survival and differentiation. The aim of this work was to investigate the role of PKC activation on retinal cells proliferation. We demonstrated that PKC activation by phorbol 12-myristate 13-acetate (PMA), a tumor promoter phorbol ester, is able to decrease retinal cells proliferation. This effect was mediated by M1 receptors and dependent on intracellular Ca(2+) increase, tyrosine kinase activity, phosphatidylinositol 3-kinase activity, polypeptide secretion and activation of TrkB receptors. The effect of PMA was not via activation of mitogen-activated protein (MAP) kinase. Carbamylcholine and brain derived neurotrophic factor were both able to decrease retinal cells proliferation to the same level as PMA did. Our results suggest that PKC activation leads to a decrease in retinal cells proliferation through the release of acetylcholine and brain derived neurotrophic factor in the culture, and activation of M1 and TrkB receptors, respectively.
dos Santos
Aline Araujo
AA
Programa de Neuroimunologia, Departamento de Neurobiologia, Instituto de Biologia, Centro de Estudos Gerais, Universidade Federal Fluminense, Niterói, Rio de Janeiro 24001-970, Brazil.
Medina
Simone Vidal
SV
Sholl-Franco
Alfred
A
de Araujo
Elizabeth Giestal
EG
D000109:Acetylcholine / Q000502:physiology*; D000470:Alkaloids; D025042:Amacrine Cells / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D053119:Benzophenanthridines; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005136:Eye Proteins / Q000187:drug effects / Q000378:metabolism*; D006131:Growth Inhibitors / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D012160:Retina / Q000166:cytology / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000470:Alkaloids; D053119:Benzophenanthridines; D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D005136:Eye Proteins; D006131:Growth Inhibitors; D007527:Isoenzymes; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010617:Phenanthridines; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; C046338:telenzepine; D010890:Pirenzepine; D010095:Oxotremorine; D001285:Atropine; D002217:Carbachol; C016299:chelerythrine; D011493:Protein Kinase C; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium