Platelet activating factor-induced apoptosis is inhibited by ectopic expression of the platelet activating factor G-protein coupled receptor.
J Neurochem
; 82(6): 1502-11, 2002 Sep.
Article
in En
| MEDLINE
| ID: mdl-12354298
ABSTRACT
The pro-inflammatory lipid mediator platelet activating factor (PAF 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) accumulates in ischemia, epilepsy, and human immunodeficiency virus-1-associated dementia and is implicated in neuronal loss. The present study was undertaken to establish a role for its G-protein coupled receptor in regulating neurotoxicity. PC12 cells do not express PAF receptor mRNA as demonstrated by northern analysis and RT-PCR. In the absence of the G-protein coupled receptor, PAF (0.1-1 micro m) triggered chromatin condensation, DNA strand breaks, oligonucleosomal fragmentation, and nuclear disintegration characteristic of apoptosis. Lyso-PAF (0.001-1 micro m), the immediate metabolite of PAF, did not elicit apoptotic death. Concentrations of PAF or lyso-PAF that exceeded critical micelle concentration had physicochemical effects on plasma membrane resulting in necrosis. Apoptosis but not necrosis was inhibited by the PAF antagonist BN52021 (1-100 micro m) but not CV3988 (0.2-20 micro m). Ectopic PAF receptor expression protected PC12 transfectants from ligand-induced apoptosis. PAF receptor-mediated protection was inhibited by CV3988 (1 micro m). These data provide empirical evidence that (i) PAF can initiate apoptosis independently of its G-protein coupled receptor; (ii) PAF signaling initiated by its G-protein coupled receptor is cytoprotective to PC12 cells; (iii) the pro- and anti-apoptotic effects of PAF on PC12 cells can be pharmacologically distinguished using two different PAF antagonists.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pheochromocytoma
/
Platelet Activating Factor
/
Platelet Membrane Glycoproteins
/
Apoptosis
/
Receptors, Cell Surface
/
GTP-Binding Proteins
/
Receptors, G-Protein-Coupled
Limits:
Animals
/
Humans
Language:
En
Journal:
J Neurochem
Year:
2002
Document type:
Article
Affiliation country:
Canada