PUBLICATION

Extracellular ADP regulates lesion-induced in vivo cell proliferation and death in the zebrafish retina

Authors
Battista, A.G., Ricatti, M.J., Pafundo, D.E., Gautier, M.A., and Faillace, M.P.
ID
ZDB-PUB-090828-9
Date
2009
Source
Journal of neurochemistry   111(2): 600-613 (Journal)
Registered Authors
Keywords
zebrafish, retina, regeneration, ATP, ADP, cell proliferation
MeSH Terms
  • Adenosine/metabolism
  • Adenosine/pharmacology
  • Adenosine Diphosphate/analogs & derivatives
  • Adenosine Diphosphate/metabolism*
  • Adenosine Diphosphate/pharmacology
  • Adenosine Triphosphatases/metabolism
  • Adenosine Triphosphate/metabolism
  • Adenosine Triphosphate/pharmacology
  • Age Factors
  • Animals
  • Antimetabolites/toxicity
  • Bromodeoxyuridine/toxicity
  • Cell Death/drug effects
  • Cell Death/physiology*
  • Cell Differentiation/drug effects
  • Cell Differentiation/physiology
  • Cell Division/drug effects
  • Cell Division/physiology
  • Cell Membrane/metabolism
  • Enzyme Inhibitors/pharmacology
  • Extracellular Space/metabolism
  • Hydrolysis
  • Ouabain/pharmacology
  • Paracrine Communication/physiology
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2/metabolism
  • Receptors, Purinergic P2Y1
  • Retina/cytology*
  • Retina/metabolism*
  • Zebrafish
PubMed
19694906 Full text @ J. Neurochem.
Abstract
Regeneration and growth that occur in the adult teleost retina by neurogenesis have been helpful in identifying molecular and cellular mechanisms underlying cell proliferation and differentiation. In this report, we demonstrate that endogenous purinergic signals regulate cell proliferation induced by a cytotoxic injury of the adult zebrafish retina which mainly damages inner retinal layers. Particularly, we found that ADP, but not ATP or adenosine, significantly enhanced cell division as assessed by BrdU incorporation following injury, during the degenerative and proliferative phase of the regeneration process. This effect of ADP occurs via P2Y1 metabotropic receptors as shown by intraocular injection of selective antagonists. Additionally, we describe a role for purinergic signals in regulating cell death induced by injury. Scavenging of extracellular nucleotides significantly increased cell death principally seen in the inner retinal layers. This effect is partially reproduced by blocking P2Y1 receptors suggesting a neuroprotective function for ADP, which is derived from extracellular ATP probably released by dying cells as a consequence of the ouabain-treatment. This study demonstrates a crucial role for ADP as a paracrine signal in the repair of retinal tissue following injury.
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Human Disease / Model
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