In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 35, No. suppl_1 ( 2015-05)
Kurzfassung:
Introduction: Individuals born with intrauterine growth restriction develop cardiovascular disease. We employed hepatic microarray-based expression profiling of male rat offspring born to mothers subjected to combined intrauterine and postnatal calorie restriction (IPCR) as a discovery driven experiment to interrogate intrauterine growth restriction. These studies identified that the expression of Apobec1 and Apobec1 complementation factor (A1CF), genes known to edit apolipoprotein B (ApoB) mRNA through the epigenetic process of cytosine deamination, are decreased in IPCR. Editing of ApoB mRNA at position 666 changes the ribonucleotide base from a cytosine to a uracil (U) and controls the production of ApoB100 and ApoB48 lipoproteins. Hypothesis: IPCR decreases hepatic ApoB mRNA editing in male offspring through transcriptional regulation of Apobec1 and A1CF. Methods: Pyrosequencing designed to interrogate ApoB mRNA editing was used to quantify hepatic ApoB100 and ApoB48 transcripts in an experiment employing the male offspring (litters culled to 6 male offspring for each mother) from 4 control fed mothers and 4 mothers subjected to 50% calorie restriction from embryonic day 11 to postnatal day 21 (IPCR). RT-qPCR and western blotting were employed to quantify the hepatic expression of Apobec1 and A1CF. Serum ApoB100 and Apo48 were quantified by ELISA. Results: ApoB transcripts in the control fed offspring were edited, with a U base call of 55 ± 2% at position 666, whereas IPCR offspring possessed decreased editing with a U base call of 12 ± 1% (n=12 for each group; F=368; p 〈 0.0001). The RT-qPCR relative quotient (RQ) in the IPCR group was 0.2 ± 0.1 (F=107;p 〈 0.0001) and 0.4 ± 0.1 (F=25;p 〈 0.0001) for Apobec1 and A1CF, respectively (RQ=1 in the control fed offspring for both Apobec1 and A1CF). Relative to control, IPCR treatment significantly decreased hepatic Apobec1 and A1CF proteins by 45% ± 10 and 27 % ± 9.2 respectively. IPCR treatment increased serum ApoB100 by 1.5 fold ± 0.43 (p= 0.051) and significantly decreased ApoB48 by 0.8 fold ± 0.1 (n=6) compared to control. Conclusion: These data define a novel association of IPCR and ApoB editing through a nutritionally controlled epigenetic process working through transcriptional control of Apobec1 and A1CF.
Materialart:
Online-Ressource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.35.suppl_1.313
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2015
ZDB Id:
1494427-3
