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The repressor element-1 (RE-1) silencing transcription factor (REST) interacts with an RE-1 cis element and represses the transcription of neuron-specific genes in neuronal progenitors but is down-regulated in post-mitotic neurons. We report that REST expression is modified, in a time-dependent manner, in SH-SY5Y neuroblastoma cells exposed to insulin-like growth factor I (IGF-I), a polypeptide hormone affecting various aspects of neuronal induction and maturation. REST is increased in cells treated with IGF-I for 2 days and then declines in 5-day-treated cells concomitant with a progressive neurite extension. To investigate any role played by REST in neurodifferentiation by IGF-I, we employed an antisense oligonucleotide (AS-ODN) complementary to REST mRNA. In AS-ODN-treated cells, the effects elicited by IGF-I on cell proliferation are not influenced whereas a marked decrease of REST significantly increases neurite elongation without any gross perturbation of neurogenesis. Synapsin I and betaIII-tubulin gene promoters contain an RE-1 motif and their transcription is repressed by REST; both of them are increased in cells exposed to IGF-I for 5 days and further elevated by AS-ODN treatment. A parallel increase of growth cone-associated protein 43, a protein chosen as a neuronal marker not directly regulated by REST, is also observed. Therefore, REST is elevated during early steps of neural induction by IGF-I and could contribute to down-regulate genes not yet required by the differentiation program while it declines later for the acquisition of neural phenotypes. These results suggest a model in which differentiating neuroblastoma cells determine their extent of neurite outgrowth on the basis of REST disappearance.

Zinc and copper status was examined in 19 healthy and 43 atopic children (22 asthmatics and 21 eczematous) 2-14 years old. Dietary intakes for energy, protein, zinc and copper and some nutritional indices (height, weight, serum protein, albumin, ceruloplasmin) were similar in the allergic and in the control group. The proton-induced X-ray fluorescence technique was used to assess zinc and copper concentrations in serum and hair. No difference was detected in serum zinc concentration between allergic and healthy children. In contrast, mean hair zinc level was lower (p less than 0.05) in allergic than in healthy children (99 +/- 6 vs. 147 +/- 9 micrograms/g). Mean serum copper content was higher in asthmatic than in control children while mean hair copper was higher (p less than 0.05) in asthmatic and eczematous children than in the control group. These findings suggest a different zinc and copper nutritional status between allergic and healthy subjects. Allergic children, in particular, seem to be a risk of zinc deficiency.