Gestational zinc deficiency affects the regulation of transcription factors AP-1, NF-κB and NFAT in fetal brain.
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.
Aimo
Lucila
L
Department of Nutrition, University of California Davis, CA 95616, USA.
Mackenzie
Gerardo G
GG
Keenan
Alison H
AH
Oteiza
Patricia I
PI
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005333:Fetus / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism*
D016328:NF-kappa B; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases; D015032:Zinc