P2Y2 receptors activate neuroprotective mechanisms in astrocytic cells

Nataliya E. Chorna, Laura I. Santiago-Pérez, Laurie Erb, Cheikh Seye, Joseph T. Neary, Grace Y. Sun, Gary A. Weisman, Fernando A. González

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Mechanical or ischemic trauma to the CNS causes the release of nucleotides and other neurotransmitters into the extracellular space. Nucleotides can activate nucleotide receptors that modulate the expression of genes implicated in cellular adaptive responses. In this investigation, we used human 1321N1 astrocytoma cells expressing a recombinant P2Y2 receptor to assess the role of this receptor in the regulation of anti-apoptotic (bcl-2 and bcl-xl) and pro-apoptotic (bax) gene expression. Acute treatment with the P2Y 2 receptor agonist UTP up-regulated bcl-2 and bcl-xl, and down-regulated bax, gene expression. Activation of P2Y2 receptors was also coupled to the phosphorylation of cyclic AMP responsive element binding protein that positively regulates bcl-2 and bcl-xl gene expression. Cyclic AMP responsive element decoy oligonucleotides markedly attenuated the UTP-induced increase in bcl-2 and bcl-xl mRNA levels. Activation of P2Y2 receptors induced the phosphorylation of the pro-apoptotic factor Bad and caused a reduction in bax/bcl-2 mRNA expression ratio. All these signaling pathways are known to be involved in cell survival mechanisms. Using cDNA microarray analysis and RT-PCR, P2Y2 receptors were found to up-regulate the expression of genes for neurotrophins, neuropeptides and growth factors including nerve growth factor 2; neurotrophin 3; glia-derived neurite-promoting factor, as well as extracellular matrix proteins CD44 and fibronectin precursor - genes known to regulate neuroprotection. Consistent with this observation, conditioned media from UTP-treated 1321N1 cells expressing P2Y2 receptors stimulated the outgrowth of neurites in PC-12 cells. Taken together, our results suggest an important novel role for the P2Y2 receptor in survival and neuroprotective mechanisms under pathological conditions.

Original languageEnglish (US)
Pages (from-to)119-132
Number of pages14
JournalJournal of Neurochemistry
Volume91
Issue number1
DOIs
StatePublished - Oct 2004
Externally publishedYes

Fingerprint

Purinergic P2Y2 Receptors
Uridine Triphosphate
Gene Expression
Gene expression
Neurotrophin 3
Phosphorylation
Nucleotides
Genes
Cells
Cyclic AMP
Chemical activation
Messenger RNA
Extracellular Matrix Proteins
Astrocytoma
Nerve Growth Factors
Extracellular Space
Microarray Analysis
Microarrays
Conditioned Culture Medium
Oligonucleotide Array Sequence Analysis

Keywords

  • Astrocytes
  • Gene expression
  • P2Y nucleotide receptor
  • Purinergic signaling

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Chorna, N. E., Santiago-Pérez, L. I., Erb, L., Seye, C., Neary, J. T., Sun, G. Y., ... González, F. A. (2004). P2Y2 receptors activate neuroprotective mechanisms in astrocytic cells. Journal of Neurochemistry, 91(1), 119-132. https://doi.org/10.1111/j.1471-4159.2004.02699.x

P2Y2 receptors activate neuroprotective mechanisms in astrocytic cells. / Chorna, Nataliya E.; Santiago-Pérez, Laura I.; Erb, Laurie; Seye, Cheikh; Neary, Joseph T.; Sun, Grace Y.; Weisman, Gary A.; González, Fernando A.

In: Journal of Neurochemistry, Vol. 91, No. 1, 10.2004, p. 119-132.

Research output: Contribution to journalArticle

Chorna, NE, Santiago-Pérez, LI, Erb, L, Seye, C, Neary, JT, Sun, GY, Weisman, GA & González, FA 2004, 'P2Y2 receptors activate neuroprotective mechanisms in astrocytic cells', Journal of Neurochemistry, vol. 91, no. 1, pp. 119-132. https://doi.org/10.1111/j.1471-4159.2004.02699.x
Chorna, Nataliya E. ; Santiago-Pérez, Laura I. ; Erb, Laurie ; Seye, Cheikh ; Neary, Joseph T. ; Sun, Grace Y. ; Weisman, Gary A. ; González, Fernando A. / P2Y2 receptors activate neuroprotective mechanisms in astrocytic cells. In: Journal of Neurochemistry. 2004 ; Vol. 91, No. 1. pp. 119-132.
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