Human group III secreted phospholipase A2 promotes neuronal outgrowth and survival.
Human sPLA2-III [group III secreted PLA2 (phospholipase A2)] is an atypical sPLA2 isoenzyme that consists of a central group III sPLA2 domain flanked by unique N- and C-terminal domains. In the present study, we found that sPLA2-III is expressed in neuronal cells, such as peripheral neuronal fibres, spinal DRG (dorsal root ganglia) neurons and cerebellar Purkinje cells. Adenoviral expression of sPLA2-III in PC12 cells (pheochromocytoma cells) or DRG explants facilitated neurite outgrowth, whereas expression of a catalytically inactive sPLA2-III mutant or use of sPLA2-III-directed siRNA (small interfering RNA) reduced NGF (nerve growth factor)-induced neuritogenesis. sPLA2-III also suppressed neuronal death induced by NGF deprivation. Lipid MS revealed that sPLA2-III overexpression increased the cellular level of lysophosphatidylcholine, a PLA2 reaction product with neuritogenic and neurotropic activities, whereas siRNA knockdown reduced the level of lysophosphatidylcholine. These observations suggest the potential contribution of sPLA2-III to neuronal differentiation and its function under certain conditions.
Masuda
Seiko
S
Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
Yamamoto
Kei
K
Hirabayashi
Tetsuya
T
Ishikawa
Yukio
Y
Ishii
Toshiharu
T
Kudo
Ichiro
I
Murakami
Makoto
M
D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival / Q000528:radiation effects; D018076:DNA, Complementary / Q000378:metabolism; D054520:Group III Phospholipases A2 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000378:metabolism; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000201:enzymology*; D016716:PC12 Cells; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
D018076:DNA, Complementary; D034741:RNA, Small Interfering; D020932:Nerve Growth Factor; D054520:Group III Phospholipases A2