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Rat α 2 ‐macroglobulin inhibits NGF‐promoted neurite outgrowth, TrK phosphorylation, and gene expression of pheochromocytoma PC12 cells
Author(s) -
Lee PaekGyu,
Koo Peter H.
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990915)57:6<872::aid-jnr13>3.0.co;2-i
Subject(s) - neurite , nerve growth factor , tropomyosin receptor kinase a , trk receptor , signal transduction , phosphorylation , biology , microbiology and biotechnology , receptor , gene expression , endocrinology , medicine , gene , biochemistry , in vitro
Rat alpha‐1‐macroglobulin (α 1 M) and alpha‐2‐macroglobulin (α 2 M) are murine homologs of human α 2 M, and rat α 2 M is generally known as an acute‐phase protein. Monoamine‐activated forms of human α 2 M have been shown to inhibit various neuronal functions, but the effect of rat α 1 M and acute‐phase α 2 M on neurons is largely unknown. In this report, rat serotonin‐activated α 2 M (5HT‐α 2 M) has been demonstrated to inhibit nerve growth factor (NGF)‐promoted neurite extension in pheochromocytoma PC12 cells, and we investigated its possible mechanism of action including its effect on NGF‐promoted signal transduction and gene expression in these cells. Especially in the absence of NGF, 5HT‐α 2 M was found to bind to TrkA (the high‐affinity receptor for NGF) much better than normal α 2 M (N‐α 2 M). 5HT‐α 2 M dose‐dependently inhibited NGF‐promoted autophosphorylation of TrkA, and decreased the expression of two immediate‐early genes (NGFI‐A and c‐jun ) and two delayed‐response genes (SCG10 and transin) which are associated with neurite outgrowth in PC12 cells. The unmodified N‐α 2 M, on the other hand, exhibited very little or no inhibitory effects on neurite extension, Trk phosphorylation, or expression of these genes. The results of this study taken together suggest that monoamine‐activated acute‐phase rat α 2 M appears to inhibit neurite outgrowth in PC12 cells possibly via its direct binding to TrkA and subsequent blocking of TrkA‐mediated signal transduction and gene expression. J. Neurosci. Res. 57:872–883, 1999. © 1999 Wiley‐Liss, Inc.