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  • Heterogeneity in the sn-1 carbon chain of platelet-activating factor glycerophospholipids determines pro- or anti-apoptotic signaling in primary neurons.

Heterogeneity in the sn-1 carbon chain of platelet-activating factor glycerophospholipids determines pro- or anti-apoptotic signaling in primary neurons.

Journal of lipid research (2008-06-14)
Scott D Ryan, Cory S Harris, Casey L Carswell, John E Baenziger, Steffany A L Bennett
ABSTRACT

The platelet-activating factor (PAF) family of glycerophospholipids accumulates in damaged brain tissue following injury. Little is known about the role of individual isoforms in regulating neuronal survival. Here, we compared the neurotoxic and neuroprotective activities of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16-PAF) and 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine (C18-PAF) in cerebellar granule neurons. We find that both C16-PAF and C18-PAF cause PAF receptor-independent death but signal through different pathways. C16-PAF activates caspase-7, whereas C18-PAF triggers caspase-independent death in PAF receptor-deficient neurons. We further show that PAF receptor signaling is either pro- or anti-apoptotic, depending upon the identity of the sn-1 fatty acid of the PAF ligand. Activation of the PAF G-protein-coupled receptor (PAFR) by C16-PAF stimulation is anti-apoptotic and inhibits caspase-dependent death. Activation of PAFR by C18-PAF is pro-apoptotic. These results demonstrate the importance of the long-chain sn-1 fatty acid in regulating PAF-induced caspase-dependent apoptosis, caspase-independent neurodegeneration, and neuroprotection in the presence or absence of the PAF receptor.

MATERIALS
Product Number
Brand
Product Description

Avanti
C18-02:0 PC, Avanti Research - A Croda Brand 878114P, powder
Sigma-Aldrich
β-Acetyl-γ-O-hexadecyl-L-α-phosphatidylcholine hydrate, ≥98%
Avanti
C16-18:1 PC, Avanti Research - A Croda Brand 878112P, powder