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Multiple Neurotrophic Factors from Skeletal Muscle: Demonstration of Effects of Basic Fibroblast Growth Factor and Comparisons with the 22‐Kilodalton Choline Acetyltransferase Development Factor
Author(s) -
McManaman James,
Crawford Frances,
Clark Robin,
Richker Jeffrey,
Fuller Forrest
Publication year - 1989
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 - 10.1111/j.1471-4159.1989.tb09241.x
Subject(s) - choline acetyltransferase , basic fibroblast growth factor , cholinergic , neurotrophic factors , skeletal muscle , spinal cord , biology , growth factor , cholinergic neuron , nerve growth factor , medicine , endocrinology , microbiology and biotechnology , neuroscience , biochemistry , receptor
Extracts of skeletal muscle contain chromato‐graphically distinct molecules that enhance the cholinergic development of cultured embryonic rat spinal cord neurons. We have recently purified a 20–22 kilodalton anionic polypeptide choline acetyltransferase (ChAT) development factor (CDF) from rat skeletal muscle extracts that stimulates the development of ChAT activity in rat spinal cord cultures. The maximum increase in the level of ChAT activity achieved by this factor, however, is less than that achieved by the addition of the crude extract. We now show that muscle extract also contains mitogenic activity that is immunologically related to basic fibroblast growth factor (bFGF) and also that recombinant bFGF stimulates ChAT development in rat spinal cord cultures. bFGF, however, differs from CDF in its physicochemical, chromatographic, and immunological properties and by its action on nonneuronal cells. Individually, CDF and bFGF each enhance the level of ChAT activityin rat spinal cord cultures two‐ to threefold after 2 days of treatment. However, their combined actions result in a five‐to sixfold enhancement of ChAT activity, suggesting that they are affecting cholinergic development through different means. The demonstration that extracts of rat skeletal muscle contain two biochemically and immunologically distinct polypeptides, with additive effects on cultured embryonic spinal cord neurons, provides additional evidence for the involvement of multiple target‐derived neurotrophic factors in the regulation of cholinergic development