Gestational zinc deficiency affects the regulation of transcription factors AP-1, NF-κB and NFAT in fetal brain

Lucila Aimo, Gerardo Mackenzie, Alison H. Keenan, Patricia I. Oteiza

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Transcription factors AP-1, nuclear factor κB (NF-κB) and NFAT are central to brain development by regulating the expression of genes that modulate cell proliferation, differentiation, apoptosis and synaptic plasticity. This work investigated the consequences of feeding zinc-deficient and marginal zinc diets to rat dams during gestation on the modulation of AP-1, NF-κB and NFAT in fetal brain. Sprague-Dawley rats were fed from gestation day (GD) 0 a control diet ad libitum (25 μg zinc/g diet, C), a zinc-deficient diet ad libitum (0.5 μg zinc/g diet, ZD), the control diet in the amounts eaten by the ZD rats (restrict fed, RF) or a diet containing a marginal zinc concentration ad libitum (10 μg zinc/g diet, MZD) until GD 19. AP-1-DNA binding was higher (50-190%) in nuclear fraction isolated from ZD, RF and MZD fetal brains compared to controls. In MZD fetal brain, high levels of activation of the upstream mitogen-activated protein kinases JNK and p38 and low levels of ERK phosphorylation were observed. Total levels of NF-κB and NFAT activation were higher or similar in the ZD and MZD groups than in controls, respectively. However, NF-κB- and NFAT-DNA binding in nuclear fractions was markedly lower in ZD and MZD fetal brain than in controls (50-80%). The latter could be related to zinc deficiency-associated alterations of the cytoskeleton, which is required for NF-κB and NFAT nuclear transport. In summary, suboptimal zinc nutrition during gestation could cause long-term effects on brain function, partially through a deregulation of transcription factors AP-1, NF-κB and NFAT.

Original languageEnglish (US)
Pages (from-to)1069-1075
Number of pages7
JournalJournal of Nutritional Biochemistry
Volume21
Issue number11
DOIs
StatePublished - Nov 2010

Keywords

  • AP-1
  • Brain
  • Gestation
  • NF-κB
  • NFAT
  • Zinc

ASJC Scopus subject areas

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

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