Signal transduction pathways associated with ATP‐induced proliferation of cell progenitors in the intact embryonic retina

Nunes, Patricia Helena Castro; Calaza, Karin da Costa; Albuquerque, Lidiane Martins; Fragel-Madeira, Lucianne; Sholl‐Franco, Alfred; Ventura, Ana Lúcia Marques

doi:10.1016/j.ijdevneu.2007.09.007

Cited by 36 publications

(30 citation statements)

References 39 publications

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“…Although affecting different cell populations, both ADP and UTP induce cell proliferation in the early developing retina [13,20,21,23,24]. UTP also stimulates the proliferation of astrocytes from the cerebral cortex [35].…”

Section: Resultsmentioning

confidence: 99%

“…Since proliferation of retinal progenitors in the chick developing retina is stimulated by nucleotides like ADP and UTP [13,20,21,24], the growth inhibitory effect of apyrase and P2 receptor antagonists could be due to inhibition of glia proliferation in the scratched area. However, no effect of apyrase on the number of PCNA + cells was observed at the border of the scratch, suggesting that nucleotides did not affect the proliferation of these cells.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Activation of these receptors by ATP or ADP induces the proliferation of glial progenitors by a mechanism involving PKC, MAPK, and PI3K/AKT pathways [23][24][25][26]. As opposed to early developing neuronal progenitors that are sensitive to UTP, no proliferation of late developing glial progenitors is observed by activation of UTP-sensitive nucleotide receptors in monolayer cultures or cultured explants of chick embryo retinas [20,24]. The proliferative response of glial cells in culture to ATP decreases, as the cultured cells differentiate, and no effect of this nucleotide is observed 4 days after the onset of cultures obtained from retinas of 7-day-old chick embryos or 1-day-old mice [21,23].…”

Section: Introductionmentioning

confidence: 99%

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Involvement of nucleotides in glial growth following scratch injury in avian retinal cell monolayer cultures

Silva

França

Ornelas

et al. 2015

Purinergic Signalling

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When retinal cell cultures were mechanically scratched, cell growth over the empty area was observed. Only dividing and migrating, 2 M6-positive glial cells were detected. Incubation of cultures with apyrase (APY), suramin, or Reactive Blue 2 (RB-2), but not MRS 2179, significantly attenuated the growth of glial cells, suggesting that nucleotide receptors other than P2Y 1 are involved in the growth of glial cells. UTPγS but not ADPβS antagonized apyrase-induced growth inhibition in scratched cultures, suggesting the participation of UTP-sensitive receptors. No decrease in proliferating cell nuclear antigen (PCNA + ) cells was observed at the border of the scratch in apyrase-treated cultures, suggesting that glial proliferation was not affected. In apyrase-treated cultures, glial cytoplasm protrusions were smaller and unstable. Actin filaments were less organized and alfa-tubulinlabeled microtubules were mainly parallel to scratch. In contrast to control cultures, very few vinculin-labeled adhesion sites could be noticed in these cultures. Increased Akt and ERK phosphorylation was observed in UTP-treated cultures, effect that was inhibited by SRC inhibitor 1 and PI3K blocker LY294002. These inhibitors and the FAK inhibitor PF573228 also decreased glial growth over the scratch, suggesting participation of SRC, PI3K, and FAK in UTP-induced growth of glial cells in scratched cultures. RB-2 decreased dissociated glial cell attachment to fibronectin-coated dishes and migration through transwell membranes, suggesting that nucleotides regulated adhesion and migration of glial cells. In conclusion, mechanical scratch of retinal cell cultures induces growth of glial cells over the empty area through a mechanism that is dependent on activation of UTP-sensitive receptors, SRC, PI3K, and FAK.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Involvement of nucleotides in glial growth following scratch injury in avian retinal cell monolayer cultures

Silva

França

Ornelas

et al. 2015

Purinergic Signalling

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“…In the chick embryonic tissue, while UTP, through activation of P2Y2/4 receptors, induces the proliferation of early developing precursors of ganglion, amacrine, photoreceptor, and horizontal cells [12,13], ATP, through activation of P2Y1 receptors, induces the proliferation of late developing glial/bipolar progenitors [14,16]. This effect is primarily mediated by activation of PKC, MAP kinases, and the PI3K/ AKT pathway and involves the regulation of cyclin D1 and p27 kip 1 levels [14,15,17,18].…”

Section: Introductionmentioning

confidence: 99%

ATP induces the death of developing avian retinal neurons in culture via activation of P2X7 and glutamate receptors

Anccasi

Ornelas

Cossenza

et al. 2012

Purinergic Signalling

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Previous data suggest that nucleotides are important mitogens in the developing retina. Here, the effect of ATP on the death of cultured chick embryo retina cells was investigated. In cultures obtained from retinas of 7-day-old chick embryos (E7) that were cultivated for 2 days (E7C2), both ATP and BzATP induced a ∼30 % decrease in cell viability that was time-and dose-dependent and that could be blocked by 0.2 mM oxidized ATP or 0.3 μM KN-62. An increase in cleaved caspase-3 levels and in the number of TUNELpositive cells was observed when cultures were incubated with 3 mM ATP and immunolabeling for cleaved-caspase 3 was observed over neurons but not over glial cells. ATPdependent cell death was developmentally regulated, the maximal levels being detected by E7C2-3. Nucleotides were able to increase neuronal ethidium bromide and sulforhodamine B uptake in mixed and purified neuronal cultures, an effect that was blocked by the antagonists Brilliant Blue G and oxidized ATP. In contrast, nucleotide-induced cell death was observed only in mixed cultures, but not in purified cultures of neurons or glia. ATP-induced neuronal death was blocked by the glutamatergic antagonists MK801 and DNQX and activation of P2X7 receptors by ATP decreased the uptake of [ These results suggest that ATP induces apoptosis of chick embryo retinal neurons in culture through activation of P2X7 and glutamate ionotropic receptors. Involvement of a P2X7 receptor-mediated inhibition of the glial uptake of glutamate is suggested.

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Regulation of adult neural progenitor cell functions by purinergic signaling

Tang

Illéš

2016

Glia

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Extracellular purines are signaling molecules in the neurogenic niches of the brain and spinal cord, where they activate cell surface purinoceptors at embryonic neural stem cells (NSCs) and adult neural progenitor cells (NPCs). Although mRNA and protein are expressed at NSCs/NPCs for almost all subtypes of the nucleotide-sensitive P2X/P2Y, and the nucleoside-sensitive adenosine receptors, only a few of those have acquired functional significance. ATP is sequentially degraded by ecto-nucleotidases to ADP, AMP, and adenosine with agonistic properties for distinct receptor-classes. Nucleotides/nucleosides facilitate or inhibit NSC/NPC proliferation, migration and differentiation. The most ubiquitous effect of all agonists (especially of ATP and ADP) appears to be the facilitation of cell proliferation, usually through P2Y1Rs and sometimes through P2X7Rs. However, usually P2X7R activation causes necrosis/apoptosis of NPCs. Differentiation can be initiated by P2Y2R-activation or P2X7R-blockade. A key element in the transduction mechanism of either receptor is the increase of the intracellular free Ca concentration, which may arise due to its release from intracellular storage sites (G protein-coupling; P2Y) or due to its passage through the receptor-channel itself from the extracellular space (ATP-gated ion channel; P2X). Further research is needed to clarify how purinergic signaling controls NSC/NPC fate and how the balance between the quiescent and activated states is established with fine and dynamic regulation. GLIA 2017;65:213-230.

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Signal transduction pathways associated with ATP‐induced proliferation of cell progenitors in the intact embryonic retina

Cited by 36 publications

References 39 publications

Involvement of nucleotides in glial growth following scratch injury in avian retinal cell monolayer cultures

Involvement of nucleotides in glial growth following scratch injury in avian retinal cell monolayer cultures

ATP induces the death of developing avian retinal neurons in culture via activation of P2X7 and glutamate receptors

Regulation of adult neural progenitor cell functions by purinergic signaling

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