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Activation of the mitogen‐activated protein kinase cascade through nitric oxide synthesis as a mechanism of neuritogenic effect of genipin in PC12h cells
Author(s) -
Yamazaki Matsumi,
Chiba Kenzo,
Mohri Tetsuro,
Hatanaka Hiroshi
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00533.x
Subject(s) - genipin , neurite , mapk/erk pathway , microbiology and biotechnology , nitric oxide , chemistry , protein kinase a , nitric oxide synthase , kinase , mitogen activated protein kinase 3 , biochemistry , biology , in vitro , organic chemistry , chitosan
Prominent neurite outgrowth induced by genipin, a plant‐derived iridoid, was substantially inhibited by addition of N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME), a nitric oxide (NO) synthase (NOS) inhibitor, and carboxy‐PTIO, an NO scavenger, in PC12h cells. Increases of the NADPH‐diaphorase activity and neuronal and inducible NOS proteins in cells preceded the neurite outgrowth after addition of genipin to medium. NO donors could induce the neurite outgrowth dose‐dependently in the cells. On the other hand, an inhibitor of soluble guanylate cyclase (SGC), which is known to be a stimulatory target of NO, abolished greatly the genipin‐induced neurite outgrowth. Addition of extracellular signal‐regulated kinase (ERK) kinase inhibitors could almost completely abolish the neurite induction. l ‐NAME remarkably depressed genipin‐stimulated phosphorylation of ERK‐1 and ‐2. A neuritogenic effect of nerve growth factor (NGF) in PC12h cells was also remarkably inhibited by the NOS inhibitor, NO scavenger and SGC inhibitor. These findings suggest that induced NO production followed by cyclic GMP‐mediated stimulation of the mitogen‐activated protein kinase (MAPK) cascade is implicated in the neuritogenesis by genipin and NGF in PC12h cells.