Increased apoB100 mRNA in inbred strains of mice by estrogen is caused by decreased RNA editing protein mRNA.
Estrogen administration to rats diminishes all apoproteins and lipoproteins from plasma. In contrast, some inbred strains of mice raise their plasma apoB and LDL levels by more than 2-fold (Srivastava et al, 1993, Eur. J. Biochem. 216, 527-538). Further studies with 13 inbred strains of mice given 3 micrograms beta-estradiol/g body weight/day for 5 consecutive days suggest that some mouse strains increased their apoB and LDL levels and some did not. To examine the mechanism of influence of genetic factors on apoB regulation, two strains, C57L and C57BL, that increased their VLDL- and LDL-cholesterol, and 2 strains, BALB and C3H, that did not, were chosen. Estrogen increased plasma apoB levels selectively in the strains C57L and C57BL, termed as 'responders,' but did not change in BALB and C3H, termed as 'non-responders.' One of the mechanisms for increased plasma apoB levels could be through increased production of apoB-containing particles. This possibility was investigated. ApoB and REPR mRNA were quantified by RNase protection assay, and apoB-100 mRNA by apoB mRNA editing assay. Hepatic apoB mRNA increased by 30% in 'non-responders,' but decreased by 20% in the 'responders.' However, apoB-100 mRNA increased relative to apoB-48 mRNA in all the 4 strains by 50%. The mRNA for RNA editing protein (REPR) decreased in all strains, suggesting that apoB-100 mRNA increased as a result of decreased apoB mRNA editing activity. These results suggest that:(a) modulation of apoB mRNA by estrogen was strain-specific;(b) increased apoB100 mRNA in inbred strains of mice were caused by decreased apoB mRNA editing activity; and (c) the differences in the plasma apoB levels among 'responder' and 'nonresponder' strains of mice occur through mechanisms other than the apoB mRNA editing.
Srivastava
R A
RA
Department of Internal Medicine, Washington University School of Medicine, Saint Louis 63110, USA.
D000071479:APOBEC-1 Deaminase; D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000235:genetics*; D004958:Estradiol / Q000494:pharmacology*; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008074:Lipoproteins; D012333:RNA, Messenger; D013739:Testosterone; D004958:Estradiol; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse; C000605091:Apobec1 protein, rat; D003564:Cytidine Deaminase