[HTML][HTML] Subcellular origin of sphingosine 1-phosphate is essential for its toxic effect in lyase-deficient neurons

N Hagen, PP Van Veldhoven, RL Proia, H Park… - Journal of biological …, 2009 - ASBMB
Cerebellar granule cells from sphingosine 1-phosphate (S1P) lyase-deficient mice were
used to study the toxicity of this potent sphingolipid metabolite in terminally differentiated
postmitotic neurons. Based on earlier findings with the lyase-stable, semi-synthetic, cis-4-
methylsphingosine phosphate, we hypothesized that accumulation of S1P above a certain
threshold induces neuronal apoptosis. The present studies confirmed this conclusion and
further revealed that for S1P to induce apoptosis in lyase-deficient neurons it must also be …