The nerve growth factor protein (NGF) regulates neuronal cell death during the development of embryonic sensory and sympathetic neurons in the peripheral nervous system (PNS). NGF protects the rat pheochromocytoma line PC12, a useful model of NGF responsive peripheral neurons, from hydrogen peroxide, which interacts with ferrous iron to generate hydroxyl radicals. Exogenous catalase provides protection, whereas superoxide dismutase (SOD) has no effect on neuronal survival when PC12 cells are challenged with hydrogen peroxide. NGF treatment of PC12 cells increases the activity of catalase. NGF protection from hydrogen peroxide is partially abolished by aminotriazole (Az), a low molecular weight catalase inhibitor. Taken together, these data are consistent with the hypothesis that NGF protects from peroxidative events and consequent cell death via an induction of free radical detoxifying mechanisms, such as catalase activity.

Retinoic acid (RA), a naturally occurring metabolite of vitamin A, increased the number of receptors for nerve growth factor (NGF) in cultured human neuroblastoma cells (LA-N-1), as indicated by an immunofluorescence assay of cell surface receptors and by specific binding of 125I-NGF to solubilized receptors. Analysis of 125I-NGF binding showed that RA increased the number of both high affinity and low affinity receptors for NGF without affecting the equilibrium dissociation constants. Neurite outgrowth similar to that produced by NGF occurred following RA-treatment in LA-N-1 cells, in the SY5Y subclone of SK-N-SH human neuroblastoma cells and in explanted chick dorsal root ganglia (DRG). Whether morphological changes following RA treatment are directly related to the increase in NGF receptors is unknown. Data presented here are consistent with literature reports that RA modifies cell surface glycoproteins, including those that act as cell surface receptors for epidermal growth factor and insulin.

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The biological effects of nerve growth factor (NGF) have been shown to be mediated by the high-affinity form of the nerve growth factor receptor (NGF-R) in sympathetic and sensory neurons, and in PC12 cells. We report here that the central nervous system C6 rat glioma cell line likewise expresses functional high-affinity NGF-Rs. The expression of NGF-R mRNA in C6 cells can be up-regulated by cycloheximide and its own ligand, NGF; and it can be rapidly down-regulated by epidermal growth factor (EGF). Furthermore, C6 cells display NGF responsiveness by expressing c-fos mRNA within 30 minutes of treatment with NGF; and after 4-5 days of NGF exposure, C6 cells cease dividing as measured by [3H]-thymidine uptake, change shape, and reveal neurite-like processes. Scatchard analysis of [125I]-labelled NGF bound to solubilized C6 cells confirms the presence of both high- and low-affinity receptor protein. Crosslinking radiolabeled NGF to its receptor in the presence or absence of excess unlabeled NGF, followed by immunoprecipitation with monoclonal antibody (mAb) 192-IgG (a known anti-NGF-R antibody) and SDS-PAGE reveals a 100 kD band corresponding to the NGF/NGF-R complex. An identical band is observed when the immunoprecipitation is carried out with mAb 217c, suggesting that the 217c epitope is related to NGF-R. The 217c antibody was generated against C6 cells and shown to be a cell surface antibody (Peng et al., Science 215:1102-4, 1982); several investigators have used it subsequently as an immunocytochemical marker for Schwann cells. The significance of NGF-Rs in a CNS glial cell line is unclear, but association of NGF with the control of proliferation and/or differentiation of primitive glial cells is suggested.

The nerve growth factor protein (NGF) has been demonstrated to affect neuronal development and maintenance of the differentiated state in certain neurons of the peripheral and central nervous system (CNS) of mammals. In the CNS, NGF has sparing effects on cholinergic neurons of the rodent basal forebrain (BF) following lesions where it selectively induces choline acetyltransferase (ChAT). NGF also induces ChAT in the areas to which BF provides afferents. In aged rats, there is a reduction in the NGF-binding capacity of sympathetic ganglia. Here, we wish to report that there is a decrease in the NGF-binding capacity of the hippocampus and basal forebrain of aged (26-month-old) rats as compared to 4-month-old controls but no change in NGF binding in cerebellum. In all instances, equilibrium binding dissociation constants did not differ significantly. Treatment of rats with acetyl-L-carnitine, reported to improve cognitive performance of aged rats, ameliorates these age-related deficits.