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Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion

The Journal of Biomedical Research 2014年第3期28卷 178-193页

作者： Eric Fisher Elizabeth Lake Roger S McLeod Biochemistry & Molecular Biology Faculty of MedicineDalhousie University

Apolipoprotein B （apoB） is the main protein component of very low density lipoprotein （VLDL） and is necessary for the assembly and secretion of these triglyceride （TG）-rich particles. Following release from the liver, VLDL is converted to low density lipoprotein （LDL） in the plasma and increased production of VLDL can therefore play a detrimental role in cardiovascular disease. Increasing evidence has helped to establish VLDL assembly as a target for the treatment of dyslipidemias. Multiple factors are involved in the folding of the apoB protein and the formation of a secretion-competent VLDL particle. Failed VLDL assembly can initiate quality control mechanisms in the hepatocyte that target apoB for degradation. ApoB is a substrate for endoplasmic reticulum associated degradation （ERAD） by the ubiquitin proteasome system and for autophagy. Efficient targeting and disposal of apoB is a regu- lated process that modulates VLDL secretion and partitioning of TG. Emerging evidence suggests that significant overlap exists between these degradative pathways. For example, the insulin-mediated targeting of apoB to autop- hagy and postprandial activation of the unfolded protein response （UPR） may employ the same cellular machinery and regulatory cues. Changes in the quality control mechanisms for apoB impact hepatic physiology and pathology states, including insulin resistance and fatty liver. Insulin signaling, lipid metabolism and the hepatic UPR may impact VLDL production, particularly during the postprandial state. In this review we summarize our current understanding of VLDL assembly, apoB degradation, quality control mechanisms and the role of these processes in liver physiology and in pathologic states.

关键词： apolipoprotein B very low density lipoprotein proteasome ubiquitin autophagy steatosis

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Expression of Monocyte Chemoattractant Protein-1 in Monocytes and Effects of Native and Oxidized very low density lipoproteins

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1997年第4期17卷 203-205页

作者：王国平邓仲端倪娟 Department of Pathology Tongji Medical University Wuhan

Monocyte chemoattractant protein-1(MCP-1), a potent chemoattractant, is thought to play an important role in migration of monocytes into atherosclerotic lesions. The present study was designed to investigate the capacity of human peripheral blood monocytes to express MCP-1 and effects of native very low density lipoprotein (VLDL) and oxidized VLDL(OX-VLDL) on the expression. The total RNA was extracted from cultured monocytes, which were exposed to VLDL and OX-VLDL, and the media conditioned by monocytes were collected. MCP-1 mRNA expression was examined by Northern blot analysis. MCP-1 protein in conditioned media was determined by using sandwich ELISA. The results showed that monocytes can express MCP-1 after a 24 h incubation at 37℃，and the expression was markedly increased by a exposure to OX-VLDL, whereas the expression was slightly increased when exposed to VLDL. It suggests that the capacity of monocytes to produce MCP-1 that recruits and activates circulating monocytes may be of considerable importance in atherogenesis, and oxidation of VLDL enhances its potential to promote atherogenesis.

关键词： monocyte chemoattractant protein-1 very low density lipoprotein oxidization monocytes atherosclerosis

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Effect of Divergent Selection for Plasma very low Denstity lipoprotein Concentration on Reproductive Performance in Broiler Chickens

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Journal of Northeast Agricultural University(English Edition) 1998年第1期5卷 29-39页

作者： ChenJinwen ZhaoHeshan DepartmentofAnimalSciences NortheastAgricultualUniversityHarbin150030PRC InstituteofAnimalSciences GAASGuangzhou510640PRC

The reproductive performance and abdominal fat of the high VLDL (H-VLDL) and low VLDL (L-VLDL) lines were studied after divergent selection for plasma very low density lipoprotein (VLDL) concentration in broiler chickens at 8 weeks of age. It was shown that the main reproductive traits were higher in L-VLDL line than H-VLDL line. The beneficial correlated responses of the reproductive traits were produced by the selection for plasma VLDL. 1) Plasma VLDL concentration was significantly correlated with abdominal fat (r=0.50, P<0.01), ahich was higher than that with plasma triglyceride concentration. There was a significant difference in abdominal fat between both lines but age increase or food restriction may decrease this difference. The H-VLDL line had about twice as much abdominal fat as had L-VLDL at 8 weeks of age, while its mean body weight was similar to that of the L-VLDL line from birtl to the end of laying. 2) Mortality from apparently stress-related causes by food restriction for H-VLDL line females began to increase from 15 weeks of age and was 21% (38/180) higher compared with 13% (23/180) for L-VLDL line females. 3) Age of 5% Lying for L-VLDL line was 3 days less than that of H-VLDL line, age of 50% Lying was 37 days less for L-VLDL line than H-VLDL line, and the age of laying peak was similiar in both lines. Rate of lay at peak in L-VLDL and H-VLDL lines were 70.3%, 66.4%, respectively. 4) Fertility rate in L-VLDL line was significantly higher than that of H-VLDL line at 27 weeks of age (P=0.01) and there was a little difference in fertility rates between H-VLDL and L-VLDL line during late laying period. There were no significant differences between H-VLDL and L-VLDL lines in of day-old healthy the numbers chicks and hatchabilities of fertile and total eggs wheres mean numbers of healthy day-old chicks per hen were more is L-VLDL line than in H-VLDL line. 5) Under food restriction, egg production was higher in L-VLDL line than in H-VLDL line. It sh

关键词： reproductive performance very low density lipoprotein divergent selection

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lipoprotein metabolism in nonalcoholic fatty liver disease

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The Journal of Biomedical Research 2013年第1期27卷 1-13页

作者： Zhenghui Gordon Jiang Simon C. Robson Zemin Yao Department of Medicine Beth Israel Deaconess Medical Center/Harvard Medical SchoolBostonMAUSA Division of Gastroenterology CLS612Beth Israel Deaconess Medical Center/Harvard Medical SchoolBostonMAUSA Department of Biochemistry Microbiology and ImmunologyOttawa Institute of Systems BiologyUniversity of OttawaOttawaOntario KIH 8M5Canada

Nonalcoholic fatty liver disease （NAFLD）, an pathologies characterized by fatty accumulation in escalating health problem worldwide, covers a spectrum of hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellu- lar role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metab- olism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD.

关键词： nonalcoholic fatty liver disease (NAFLD) hepatic steatosis nonalcoholic steatohepatitis apolipo-protein lipoprotein metabolism very low density lipoprotein

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