title: PMA increases M3 muscarinic receptor levels and decreases retinal cells proliferation through a change in the levels of cell-cycle regulatory proteins.
abstract: Protein kinase C (PKC) pathway plays important roles in different phenomena in nervous system development. Our previous data demonstrated that phorbol 12-myristate 13-acetate (PMA) treatment, a PKC activator, for 48 h decreases retinal cells proliferation by a mechanism mediated by muscarinic receptor activation, involving a decrease in M1 receptors levels. The aim of this work was to analyze how PMA interferes in the levels of cell cycle control proteins p53, p21 and cyclin D1 and also to investigate its influence on M3 receptor levels. Our results show that PMA (50 ng/mL) produces a significant increase in p21 and p53 levels, decreases cyclin D1 levels, and also enhances M3 receptors levels in cell cultures. Evaluating the postnatal retinal tissue development until 30 days, we observed that tissue differentiation is accompanied by an increase in M3 and p21 levels. Based on our results we suggest that PMA treatment is promoting a change in muscarinic receptors expression mimicking the pattern observed during tissue differentiation, indicating that PMA is probably accelerating the cholinergic differentiation in rat retinal cell cultures.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Instituto Biomédico, UFF, Rua Hernani Pires de Mello, 101, Niterói CEP 24210-130, RJ, Brazil.
authors.forename: Luis Eduardo Gomes
authors.initials: LE
authors.lastname: Braga
authors.forename: Marcelo Gomes
authors.initials: MG
authors.lastname: Granja
authors.forename: Gustavo Mataruna
authors.initials: GM
authors.lastname: da Silva
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Giestal-de-Araujo
authors.forename: Aline Araujo
authors.initials: AA
authors.lastname: dos Santos
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D051381:Rats; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D055351:Retinal Neurons / Q000187:drug effects* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D010703:Phorbol Esters; D043587:Receptor, Muscarinic M3; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C119222:phorbol-12-myristate
keywords: Cyclin D1; PKC; Rat; p21; p53