Neuronal expression and neuritogenic action of group X secreted phospholipase A2.
Although individual mammalian secreted phospholipase A(2) (sPLA(2)) enzymes exhibit unique tissue and cellular distributions, the cell type-specific functions of each enzyme remain largely unknown. In this study, we found by immunohistochemistry that group X sPLA(2) (sPLA(2)-X) is uniquely located in the peripheral neuronal fibers, an observation that was supported by detection of its transcript and protein in the neuronal cell line PC12 and in primary dorsal root ganglia neurons. Adenoviral expression of sPLA(2)-X in PC12 cells facilitated neurite outgrowth, particularly when combined with a suboptimal concentration of nerve growth factor. In neuronally differentiated PC12 cells, sPLA(2)-X was preferentially localized in the Golgi apparatus and growth cones, and proteolytic conversion of the proenzyme to mature enzyme mainly occurred after the secretion process. The neurite-extending ability of sPLA(2)-X depended on the production of its catalytic product, lysophosphatidylcholine. Moreover, nerve growth factor-induced neurite extension of PC12 cells was modestly but significantly attenuated by an anti-sPLA(2)-X antibody or by a small interfering RNA for sPLA(2)-X. These observations suggest the potential contribution of sPLA(2)-X to neuronal differentiation, and possibly repair, under certain conditions.
Masuda
Seiko
S
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Shinagawa-ku, Tokyo, USA.
Murakami
Makoto
M
Takanezawa
Yasukazu
Y
Aoki
Junken
J
Arai
Hiroyuki
H
Ishikawa
Yukio
Y
Ishii
Toshiharu
T
Arioka
Manabu
M
Kudo
Ichiro
I
D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002384:Catalysis; D002454:Cell Differentiation; D002460:Cell Line; D002855:Chromatography, Thin Layer; D018076:DNA, Complementary / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008244:Lysophosphatidylcholines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D020932:Nerve Growth Factor; D009474:Neurons / Q000201:enzymology* / Q000378:metabolism; D016716:PC12 Cells; D010741:Phospholipases A / Q000096:biosynthesis* / Q000378:metabolism*; D054467:Phospholipases A2; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
D018076:DNA, Complementary; D008244:Lysophosphatidylcholines; D034741:RNA, Small Interfering; D020932:Nerve Growth Factor; D010741:Phospholipases A; D054467:Phospholipases A2