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Role of nerve growth factor in suramin neurotoxicity studied in vitro
Author(s) -
Russell James W.,
Windebank Anthony J.,
Podratz Jewel L.
Publication year - 1994
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410360215
Subject(s) - suramin , nerve growth factor , neurite , neurotoxicity , receptor , in vitro , medicine , endocrinology , chemistry , pharmacology , biology , toxicity , biochemistry
We determined whether suramin neurotoxicity can be prevented by nerve growth factor (NGF) and if this interaction occurs at the level of the NGF receptor. Neurite outgrowth from rat dorsal root ganglia in vitro was measured serially in the presence of suramin (100–600 μM) alone or with β‐NGF (50–1,000 ng/ml). Competitive NGF receptor–binding studies were done with 125 I‐labeled NGF in the presence or absence of suramin. Neurite growth was inhibited in a dose‐dependent manner, but at usual neurotoxic levels this inhibition could be overcome completely by increasing the concentration of NGF. Receptor‐binding assays showed similar dose‐dependent inhibition of 125 I‐labeled NGF binding. In the presence of suramin, the dissociation constant for high‐affinity binding was decreased from 1.2 × 10 −11 to 3.9 × 10 −10 and low‐affinity binding from 2.7 × 10 −9 to 1.2 × 10 −8 . Increasing doses of suramin inhibited 125 I‐labeled NGF specific binding in a dose‐dependent fashion, and doses of suramin ± 1,000 μM were able to completely inhibit 125 I‐labeled NGF specific binding. Suramin‐induced dorsal root ganglia damage can be ameliorated by high‐dose NGF. This effect is most likely due to competition between suramin and NGF at the high‐affinity NGF receptor.