Effect of retinoic acid on nerve growth factor receptors

Abstract

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.

Identification and Characterization of a Retinoic Acid-regulated Human Homologue of the unc-33-like Phosphoprotein Gene (hUlip) from Neuroblastoma Cells

“…In the presence of biological response modifiers such as retinoic acid (RA) (3), increases in cAMP (4), phorbol esters (5), and interferons (6), the proliferation of these tumor cells is decreased, and there is an increase in neurite extension and neurotransmitter expression, and cells acquire some electrophysiologic properties similar to normal neurons. Several NB cell lines treated in vitro with RA increase Trk gene expression are induced to change the expression of several molecular markers, thus recapitulating steps of the normal embryonic development (7)(8)(9)(10). Our studies on the mechanisms of RA-induced differentiation of NB cells show that RA induces an increase in TrkB mRNA transcription as well as protein production.…”

Retinoic acid signaling in development: Tissue‐specific functions and evolutionary origins

“…For example, vitamin A deficient rat embryos exhibit defective axonal projections (White et al, 2000), and vitamin A deficient quail embryos are characterized by both defective axonal projections and impaired motoneuron outgrowth (Maden et al, 1996;Wilson et al, 2003). Moreover, RA has been shown to activate neurite outgrowth in cultures of various chicken and mouse cell types originating either from the developing CNS (Corcoran et al, 2000;Wuarin et al, 1990) or from the developing peripheral nervous system (Corcoran et al, 2000;Haskell et al, 1987;Plum and Clagett-Dame, 1996;Quinn and De Boni, 1991). Neuronal cell populations of invertebrates seem to exhibit a similar response to RA.…”

Expression of low‐affinity NGF receptor and trkB mRNA in human SH‐SY5Y neuroblastoma cells

“…Retinoic acid has consistently been shown to increase the expression of LNGFR in other cell types, including LA-N-l neuroblastoma cells [31], PC12 cells [32] and Sertoli cell line TM4 [33]. Data on the regulation of LNGFR by CAMP are more controversial.…”