| Autor: |
de Almeida-Pereira L; Department of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, Brazil., Repossi MG; Department of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, Brazil., Magalhães CF; Department of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, Brazil., Azevedo RF; Department of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, Brazil., Corrêa-Velloso JDC; Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil., Ulrich H; Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil., Ventura ALM; Department of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, Brazil., Fragel-Madeira L; Department of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, Brazil. lfragel@id.uff.br. |
| Abstrakt: |
Adenine nucleotides through P2Y 1 receptor stimulation are known to control retinal progenitor cell (RPC) proliferation by modulating expression of the p57 KIP2 , a cell cycle regulator. However, the role of Gi protein-coupled P2Y 12 and P2Y 13 receptors also activated by adenine nucleotides in RPC proliferation is still unknown. Gene expression of the purinergic P2Y 12 subtype was detected in rat retina during early postnatal days (P0 to P5), while expression levels of P2Y 13 were low. Immunohistochemistry assays performed with rat retina on P3 revealed P2Y 12 receptor expression in both Ki-67-positive cells in the neuroblastic layer and Ki-67-negative cells in the ganglion cell layer and inner nuclear layer. Nonetheless, P2Y 13 receptor expression could not be detected in any stratum of rat retina. Intravitreal injection of PSB 0739 or clopidogrel, both selective P2Y 12 receptor antagonists, increased by 20 and 15%, respectively, the number of Ki-67-positive cells following 24 h of exposure. Moreover, the P2Y 12 receptor inhibition increased cyclin D1 and decreased p57 KIP2 expression. However, there were no changes in the S phase of the cell cycle (BrdU-positive cells) or in mitosis (phospho-histone-H3-positive cells). Interestingly, an increase in the number of cyclin D1/TUNEL-positive cells after treatment with PSB 0739 was observed. These data suggest that activation of P2Y 12 receptors is required for the successful exit of RPCs from cell cycle in the postnatal rat retina. |
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