Lysophosphatidylcholine protects cerebellar granule neurons from apoptotic cell death

Journal of Neuroscience Research
Yutaka IkenoManabu Arioka

Abstract

Cultured cerebellar granule neurons (CGNs) undergo apoptosis when deprived of depolarizing stimulation and provide an in vitro model system with which to study the effects of neurotrophic substances. Our previous results showed that secretory phospholipases A(2) (sPLA(2)s) protect CGNs from apoptotic cell death under the nondepolarizing condition. In this study, we further analyzed the mechanism whereby sPLA(2) exhibits this effect. Among the primary metabolites of sPLA(2) tested, lysophosphatidylcholine (LPC), but not other lysophospholipids, remarkably rescued CGNs from apoptosis. In contrast, neither arachidonic nor oleic acids displayed neurotrophic effect. Release of LPC into the culture media occurred in response to sPLA(2) treatment, and degradation or sequestration of LPC attenuated the survival-promoting effects of sPLA(2) and LPC. The neurotrophic effect of LPC required the presence of extracellular Ca(2+) and L-type Ca(2+) channel activity, suggesting that Ca(2+) influx across the plasma membrane is evoked by LPC. sPLA(2)- or LPC-induced promotion of CGN survival was suppressed by inhibitors of protein kinase A and phospholipase C, suggesting that they play a role in mediating survival-promoting signal of sPLA(2). Th...Continue Reading

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Citations

Dec 10, 2013·Bioscience, Biotechnology, and Biochemistry· Wuhanqimuge, Manabu Arioka
Oct 5, 2010·Biochimica Et Biophysica Acta·Massimo Crimi, Mauro Degli Esposti
Nov 15, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yanyan ZhouBaolin Bian
Feb 23, 2020·Life Sciences·Panpan LiuCong Peng

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