Zinc deficiency affects the STAT1/3 signaling pathways in part through redox-mediated mechanisms.

Zinc deficiency affects the development of the central nervous system (CNS) through mechanisms only partially understood. We previously showed that zinc deficiency causes CNS oxidative stress, damaging microtubules and impairing protein nuclear shuttling. and transcription factors, which require nuclear import for their functions, play major roles in CNS development. Thus, we investigated whether zinc deficiency disrupts duanyu18131 and duanyu18133 signaling pathways in the developing fetal CNS, characterizing the involvement of oxidative stress and the cytoskeleton in the adverse effects. Maternal (gestation day 0-19) marginal zinc deficiency (MZD) reduced duanyu18131 and duanyu18133 tyrosine phosphorylation and their nuclear translocation in the embryonic day 19 (E19) rat brain. Similar effects were observed in zinc depleted IMR-32 neuroblastoma cells, with an associated decrease in and gene transactivation. Zinc deficiency caused oxidative stress (increased 4-hydroxynonenal-protein adducts) in E19 brain and IMR-32 cells, which was prevented in cells by supplementation with 0.5mM α-lipoic acid (LA). In zinc depleted IMR-32 cells, the low tyrosine phosphorylation of but not that of recovered upon incubation with LA. duanyu18131 and duanyu18133 nuclear transports were also restored by LA. Accordingly, chemical disruption of the cytoskeleton partially reduced duanyu18131 and duanyu18133 nuclear levels. In summary, the redox-dependent tyrosine phosphorylation, and oxidant-mediated disruption of the cytoskeleton are involved in the deleterious effects of zinc deficit on duanyu18131 and duanyu18133 activation and nuclear translocation. Therefore, disruption of the duanyu18131 and duanyu18133 signaling pathways may in part explain the deleterious effects of maternal MZD on fetal brain development.

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