Secretory phospholipases A2 induce neurite outgrowth in PC12 cells through lysophosphatidylcholine generation and activation of G2A receptor.
We previously demonstrated that secretory phospholipase A2 (sPLA2) and lysophosphatidylcholine (LPC) exhibit neurotrophin-like neuritogenic activity in the rat pheochromocytoma cell line PC12. In this study, we further analyzed the mechanism whereby sPLA2 displays neurite-inducing activity. Exogenously added mammalian group X sPLA2 (sPLA2-X), but not group IB and IIA sPLA2s, induced neuritogenesis, which correlated with the ability of sPLA2-X to liberate LPC into the culture media. In accordance, blocking the effect of LPC by supplementation of bovine serum albumin or phospholipase B attenuated neuritogenesis by sPLA2 or LPC. Overproduction or suppression of G2A, a G-protein-coupled receptor involved in LPC signaling, resulted in the enhancement or reduction of neuritogenesis induced by sPLA2 treatment. These results indicate that the neuritogenic effect of sPLA2 is mediated by generation of LPC and subsequent activation of G2A.
Ikeno
Yutaka
Y
Department of Biotechnology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Konno
Naoko
N
Cheon
So-hyun
SH
Bolchi
Angelo
A
Ottonello
Simone
S
Kitamoto
Katsuhiko
K
Arioka
Manabu
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002417:Cattle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D003470:Culture Media / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D054501:Group II Phospholipases A2; D054509:Group X Phospholipases A2; D015151:Immunoblotting; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008245:Lysophospholipase / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D016716:PC12 Cells; D010741:Phospholipases A / Q000378:metabolism / Q000502:physiology*; D054467:Phospholipases A2; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012709:Serum Albumin / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
D020746:Calcium Channels, L-Type; D018797:Cell Cycle Proteins; D003470:Culture Media; D018076:DNA, Complementary; C115270:G2A receptor; D008244:Lysophosphatidylcholines; D043562:Receptors, G-Protein-Coupled; D012709:Serum Albumin; D049452:Green Fluorescent Proteins; D009529:Nicardipine; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054509:Group X Phospholipases A2; D054467:Phospholipases A2; C516366:Pla2g10 protein, mouse; C516367:Pla2g10 protein, rat; D008245:Lysophospholipase; D011188:Potassium