Zinc Deficiency Disrupts Extracellular Signal-Regulated Kinase Signaling Leading to Impaired Neural Progenitor Cell Proliferation

NUTTALL, J.R; SUPASAI, S.; KHA, J.; VAETH, B.M.; MACKENZIE, G.G.; ADAMO, A.M.; OTEIZA, P.I.

JOURNAL OF NUTRITIONAL BIOCHEMISTRY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2015

0955-2863

This study investigated the mechanisms underlying altered extracellular signal-regulated kinase(ERK1/2) signaling and neural progenitor cell (NPC) proliferation associated with zinc deficiencyduring fetal brain development. Pregnant rats were fed a marginally zinc deficient or adequate dietfrom the beginning of gestation until embryonic day (E)19. Immunostaining for phosphorylatedERK1/2 in the cerebral cortex was decreased by marginal zinc deficiency and this effect wasstrongest in the ventricular zone. Furthermore, the proportion of proliferating cells in theventricular zone was decreased by marginal zinc deficiency. However phosphorylation of theupstream mitogen activated ERK kinases (MEK1/2) was not affected, suggesting that marginalzinc deficiency may have increased ERK-directed phosphatase activity. Similar results wereobserved in cultured rat cortical neural progenitor cells and in IMR-32 neuroblastoma cells, inwhich zinc-deficiency decreased ERK1/2 phosphorylation without affecting MEK1/2phosphorylation. Indeed, zinc deficiency increased the activity of the ERK-directed phosphataseprotein phosphatase 2A (PP2A) in IMR-32 cells. Furthermore, inhibition of PP2A with okadaicacid prevented the decrease in ERK phosphorylation and cell proliferation of zinc deficient IMR-32 cells. Together these results support the hypothesis that decreased zinc availability causesERK1/2 downregulation as a consequence of PP2A activation leading to a decrease in NPCproliferation