Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.4.37 (
CNPase
)
539
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The P2Y-like receptor
GPR17
is expressed by adult neural progenitor cells, suggesting a role in lineage determination. Here, we characterized
GPR17
expression and function in mouse cortical primary astrocytes/precursor cell cultures.
GPR17
is expressed by a subpopulation of oligodendrocyte precursor cells (OPCs), but not by astrocytes. This expression pattern was also confirmed in vivo. In vitro,
GPR17
expression was markedly influenced by culturing conditions. In the presence of growth factors (GFs), no significant
GPR17
expression was found. When cultures were shifted to a differentiating medium, a dramatic, time-dependent increase in the number of highly branched
GPR17
-positive cells was observed. Under these conditions,
GPR17
was induced in the totality of O4-positive immature oligodendrocytes. Instead, in cultures originally grown in the absence of GFs,
GPR17
was already expressed in morphologically more mature OPCs. Shifting of these cultures to differentiating conditions induced
GPR17
only in a subpopulation of O4-positive cells. Under both culture protocols, appearance of more mature
CNPase
- and MBP-positive cells was associated to a progressive loss of
GPR17
.
GPR17
expression also sensitized cells to adenine nucleotide-induced cytotoxicity, whereas activation with uracil nucleotides promoted differentiation towards a more mature phenotype. We suggest that GFs may keep OPCs in a less differentiated stage by restraining
GPR17
expression, and that, under permissive conditions,
GPR17
contributes to OPCs differentiation. However, upon high extracellular adenine nucleotide concentrations, as during trauma and ischemia,
GPR17
sensitizes cells to cytotoxicity. This double-edged sword role may be exploited to unveil new therapeutic approaches to acute and chronic brain disorders.
...
PMID:Expression of the new P2Y-like receptor GPR17 during oligodendrocyte precursor cell maturation regulates sensitivity to ATP-induced death. 2126 45