Srivastava R A
Department of Internal Medicine, Washington University School of Medicine, Saint Louis 63110, USA.
Biochem Biophys Res Commun. 1995 Jul 17;212(2):381-7. doi: 10.1006/bbrc.1995.1981.
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.
给大鼠注射雌激素会降低血浆中的所有载脂蛋白和脂蛋白。相比之下，一些近交系小鼠的血浆载脂蛋白B（apoB）和低密度脂蛋白（LDL）水平会升高两倍以上（Srivastava等人，1993年，《欧洲生物化学杂志》216卷，527 - 538页）。对13个近交系小鼠进行的进一步研究显示，连续5天每天按3微克β-雌二醇/克体重的剂量给药后，一些小鼠品系的apoB和LDL水平升高了，而一些则没有。为了研究遗传因素对apoB调节的影响机制，选取了两个使极低密度脂蛋白（VLDL）和LDL胆固醇升高的品系C57L和C57BL，以及两个未升高的品系BALB和C3H。雌激素选择性地提高了C57L和C57BL品系（称为“反应者”）的血浆apoB水平，但在BALB和C三H品系（称为“无反应者”）中没有变化。血浆apoB水平升高的一种机制可能是含apoB颗粒的产生增加。对此可能性进行了研究。通过核糖核酸酶保护试验对apoB和RNA编辑蛋白相关蛋白（REPR）mRNA进行定量，通过apoB mRNA编辑试验对apoB - 100 mRNA进行定量。“无反应者”肝脏中的apoB mRNA增加了30%，而“反应者”中则减少了20%。然而，在所有4个品系中，apoB - 100 mRNA相对于apoB - 48 mRNA增加了50%。RNA编辑蛋白（REPR）的mRNA在所有品系中均减少，这表明apoB - 100 mRNA增加是由于apoB mRNA编辑活性降低所致。这些结果表明：（a）雌激素对apoB mRNA的调节具有品系特异性；（b）近交系小鼠中apoB100 mRNA的增加是由apoB mRNA编辑活性降低引起的；（c）“反应者”和“无反应者”小鼠品系之间血浆apoB水平的差异是通过apoB mRNA编辑以外的机制产生的。
