Gestational marginal zinc deficiency impaired fetal neural progenitor cell proliferation by disrupting the ERK1/2 signaling pathway

Johnathan R. Nuttall, Suangsuda Supasai, Jennifer Kha, Brandon M. Vaeth, Gerardo Mackenzie, Ana M. Adamo, Patricia I. Oteiza

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

This study investigated if a marginal zinc deficiency during gestation in rats could affect fetal neural progenitor cell (NPC) proliferation through a down-regulation of the extracellular signal-regulated kinase (ERK1/2) signaling pathway. Rats were fed a marginally zinc-deficient or adequate diet from the beginning of gestation until embryonic day (E)19. The proportion of proliferating cells in the E19 fetal ventricular zone was decreased by marginal zinc deficiency. Immunostaining for phosphorylated ERK1/2 in the cerebral cortex was decreased in the marginal zinc fetuses, and this effect was strongest in the ventricular zone. Furthermore, phosphorylation of the upstream mitogen-activated ERK kinases (MEK1/2) was not affected, suggesting that marginal zinc deficiency could have increased ERK-directed phosphatase activity. Similar findings were observed in cultured rat embryonic cortical neurons and in IMR-32 neuroblastoma cells, in which zinc-deficiency decreased ERK1/2 phosphorylation without affecting MEK1/2 phosphorylation. Indeed, zinc deficiency increased the activity of the ERK-directed phosphatase protein phosphatase 2A (PP2A) in the fetal cortex and IMR-32 cells. Inhibition of PP2A with okadaic acid prevented the decrease in ERK phosphorylation and proliferation of zinc-deficient IMR-32 cells. Together these results demonstrated that decreased zinc availability reduces ERK1/2 signaling and decreased NPC proliferation as a consequence of PP2A activation. Disruption of fetal neurogenesis could underlie irreversible neurobehavioral impairments observed after even marginal zinc nutrition during a critical period of early brain development.

Original languageEnglish (US)
Pages (from-to)1116-1123
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume26
Issue number11
DOIs
StatePublished - Nov 1 2015

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MAP Kinase Signaling System
Cell proliferation
Zinc
Stem Cells
Cell Proliferation
Phosphorylation
Protein Phosphatase 2
Rats
Nutrition
Phosphoric Monoester Hydrolases
Pregnancy
Okadaic Acid
Mitogen-Activated Protein Kinase 1
Extracellular Signal-Regulated MAP Kinases
Neurogenesis
Phosphatases
Neuroblastoma
Mitogens
Cerebral Cortex
Neurons

Keywords

  • Cell signaling
  • Fetal brain development
  • Keywords
  • Mineral
  • Nutrition
  • Trace element

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Gestational marginal zinc deficiency impaired fetal neural progenitor cell proliferation by disrupting the ERK1/2 signaling pathway. / Nuttall, Johnathan R.; Supasai, Suangsuda; Kha, Jennifer; Vaeth, Brandon M.; Mackenzie, Gerardo; Adamo, Ana M.; Oteiza, Patricia I.

In: Journal of Nutritional Biochemistry, Vol. 26, No. 11, 01.11.2015, p. 1116-1123.

Research output: Contribution to journalArticle

Nuttall, Johnathan R. ; Supasai, Suangsuda ; Kha, Jennifer ; Vaeth, Brandon M. ; Mackenzie, Gerardo ; Adamo, Ana M. ; Oteiza, Patricia I. / Gestational marginal zinc deficiency impaired fetal neural progenitor cell proliferation by disrupting the ERK1/2 signaling pathway. In: Journal of Nutritional Biochemistry. 2015 ; Vol. 26, No. 11. pp. 1116-1123.
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