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Inhibitors of nitric oxide synthase attenuate nerve growth factor‐mediated increases in choline acetyltransferase expression in PC12 cells
Author(s) -
Kalisch Bettina E.,
Bock Nicholas A.,
Davis Wanda L.,
Rylett R. Jane
Publication year - 2002
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.1471-4159.2002.00854.x
Subject(s) - nerve growth factor , choline acetyltransferase , nitric oxide synthase , nitric oxide , neurite , cholinergic , medicine , endocrinology , neurotrophin , neurotrophic factors , cholinergic neuron , signal transduction , chemistry , biology , microbiology and biotechnology , receptor , biochemistry , in vitro
NGF can regulate nitric oxide synthase (NOS) expression and nitric oxide (NO) can modulate NGF‐mediated neurotrophic responses. To investigate the role of NO in NGF‐activated expression of cholinergic phenotype, PC12 cells were treated with either the nonselective NOS inhibitor l ‐NAME ( N ω ‐nitro‐ l ‐arginine methylester) or the inducible NOS selective inhibitor MIU (s‐methylisothiourea), and the effect on NGF‐stimulated ChAT mRNA levels and ChAT specific activity was determined. NGF increased steady‐state levels of mRNA and protein for both inducible and constitutive isozymes of NOS in PC12 cells, and led to enhanced NOS activity and NO production. MIU and, to a lesser extent, l ‐NAME blocked neurite outgrowth in nerve growth factor (NGF)‐treated PC12 cells. Both l ‐NAME and MIU attenuated NGF‐mediated increases in choline transferase (ChAT)‐specific activity and prevented the increase in expression of ChAT mRNA normally produced by NGF treatment of PC12 cells. The present study indicates that NO may be involved in the modulation of signal transduction pathways by which NGF leads to increased ChAT gene expression in PC12 cells.