PMA increases M3 muscarinic receptor levels and decreases retinal cells proliferation through a change in the levels of cell-cycle regulatory proteins

NEUROSCIENCE LETTERS

卷:550

Article

Gomes Braga, Luis Eduardo^1,2  Granja, Marcelo Gomes²  da Silva, Gustavo Mataruna²  Giestal-de-Araujo, Elizabeth²  dos Santos, Aline Araujo^1,2 

[1] Univ Fed Fluminense, Inst Biomed, Dept Fisiol & Farmacol, BR-24210130 Niteroi, RJ, Brazil

[2] Univ Fed Fluminense, Inst Biol, Dept Neurobiol, Programa Neurociencias, BR-24020140 Niteroi, RJ, Brazil

关键词: PKC;    Cyclin D1;    p53;    p21;    Rat;   

DOI  :  10.1016/j.neulet.2013.06.045

来源: Elsevier

【 摘 要 】

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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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