Feingold K R, Pollock A S, Moser A H, Shigenaga J K, Grunfeld C
Department of Medicine, University of California, San Francisco, USA.
J Lipid Res. 1995 Jul;36(7):1474-82.
Recent studies have shown that the administration of endotoxin (LPS) and cytokines to Syrian hamsters increases serum cholesterol levels, hepatic cholesterol synthesis, and the activity, protein levels, and mRNA levels of hepatic HMG-CoA reductase. Despite the greater than 10-fold increase in HMG-CoA reductase mRNA levels, LPS had only minimal effects on hepatic LDL receptor mRNA levels. In the present study, we demonstrate that LPS increases the transcription rate in the liver of HMG-CoA reductase mRNA approximately 4- to 5-fold without affecting LDL receptor mRNA transcription. Most stimuli that regulate HMG-CoA reductase and LDL receptor mRNA levels also regulate, in parallel, HMG-CoA synthase and farnesyl pyrophosphate (FPP) synthetase. However, in chow-fed animals, LPS and cytokines (TNF, IL-1, TNF + IL-1) increased hepatic HMG-CoA reductase mRNA levels without increasing LDL receptor, HMG-CoA synthase, or FPP synthetase mRNA levels. The feeding of cholesterol or bile resin binders regulates the mRNA levels of HMG-CoA reductase, LDL receptor, HMG-CoA synthase, and FPP synthetase. In both cholesterol- and colestipol-fed animals, LPS increased HMG-CoA reductase mRNA levels while either decreasing or causing minimal increases in the mRNA levels of the other proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
最近的研究表明，给叙利亚仓鼠注射内毒素（LPS）和细胞因子会增加血清胆固醇水平、肝脏胆固醇合成以及肝脏HMG-CoA还原酶的活性、蛋白质水平和mRNA水平。尽管HMG-CoA还原酶mRNA水平增加了10倍以上，但LPS对肝脏低密度脂蛋白受体（LDL受体）mRNA水平的影响极小。在本研究中，我们证明LPS可使肝脏中HMG-CoA还原酶mRNA的转录速率提高约4至5倍，而不影响LDL受体mRNA的转录。大多数调节HMG-CoA还原酶和LDL受体mRNA水平的刺激也会同时调节HMG-CoA合酶和法尼基焦磷酸（FPP）合酶。然而，在喂食普通饲料的动物中，LPS和细胞因子（TNF、IL-1、TNF + IL-1）增加了肝脏HMG-CoA还原酶mRNA水平，而未增加LDL受体、HMG-CoA合酶或FPP合酶的mRNA水平。喂食胆固醇或胆汁树脂结合剂可调节HMG-CoA还原酶、LDL受体、HMG-CoA合酶和FPP合酶的mRNA水平。在喂食胆固醇和考来替泊的动物中，LPS均增加了HMG-CoA还原酶mRNA水平，而对其他蛋白质的mRNA水平则要么降低，要么仅引起极小的增加。（摘要截短至250字）
