摘要：
The aryl hydrocarbon receptor (AhR) is a period-aryl hydrocarbon receptor nuclear transporter-simple minded domain transcription factor that shares structural similarity with circadian clock genes and readily interacts with components of the molecular clock. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters behavioral circadian rhythms and represses the Period1 (Per1) gene in murine hematopoietic stem and progenitor cells. Per1 expression is driven by circadian locomotor activity cycles kaput-brain muscle ARNT-like (CLOCK-BMAL1)–dependent activation of Eboxes in the Per1 promoter. We hypothesized that the effects of AhR activation on the circadian clock are mediated by disruption of CLOCK-BMAL1 function and subsequent Per1 gene suppression. Effects of AhR activation on rhythmic Per1 transcripts were examined in livers of mice after treatment with the AhR agonist, TCDD; the molecular mechanisms of Per1 repression by AhR were determined in hepatoma cells using TCDD and β-napthoflavone as AhR activators. This study reports, for the first time, that AhR activation by TCDD alters the Per1 rhythm in the mouse liver and that Per1 gene suppression depends upon the presence of AhR. Furthermore, AhR interaction with BMAL1 attenuates CLOCK-BMAL1 activity and decreases CLOCK binding at Ebox1 and Ebox3 in the Per1 promoter. Taken together, these data suggest that AhR activation represses Per1 through disrupting CLOCK-BMAL1 activity, producing dysregulation of rhythmic Per1 gene expression. These data define alteration of the Per1 rhythm as novel signaling events downstream of AhR activation. Downregulation of Per1 could contribute to metabolic disease, cancer, and other detrimental effects resulting from exposure to certain environmental pollutants.
摘要：
Atherosclerosis is characterized by a chronic inflammatory condition that involves numerous cellular and molecular inflammatory components. A wide array of inflammatory mediators, such as cytokines and proteins produced by macrophages and other cells, play a critical role in the development and progression of the disease. ATP-binding membrane cassette transporter A1 (ABCA1) is crucial for cellular cholesterol efflux and reverse cholesterol transport (RCT) and is also identified as an important target in antiatherosclerosis treatment. Evidence from several recent studies indicates that inflammation, along with other atherogenic-related mediators, plays distinct regulating roles in ABCA1 expression. Proatherogenic cytokines such as interferon (IFN)-γ and interleukin (IL)-1β have been shown to inhibit the expression of ABCA1, while antiatherogenic cytokines, including IL-10 and transforming growth factor (TGF)-β1, have been shown to promote the expression of ABCA1. Moreover, some cytokines such as tumor necrosis factor (TNF)-α seem to regulate ABCA1 expression in species-specific and dose-dependent manners. Inflammatory proteins such as C-reactive protein (CRP) and cyclooxygenase (COX)-2 are likely to inhibit ABCA1 expression during inflammation, and inflammation induced by lipopolysaccharide (LPS) was also found to block the expression of ABCA1. Interestingly, recent experiments revealed ABCA1 can function as an antiinflammatory receptor to suppress the expression of inflammatory factors, suggesting that ABCA1 may be the molecular basis for the interaction between inflammation and RCT. This review aims to summarize recent findings on the role of inflammatory cytokines, inflammatory proteins, inflammatory lipids, and the endotoxin-mediated inflammatory process in expression of ABCA1. Also covered is the current understanding of the function of ABCA1 in modulating the immune response and inflammation through its direct and indirect antiinflammatory mechanisms including lipid transport, high-density lipoprotein (HDL) formation and apoptosis.
摘要：
Cholesterol efflux from lipid-loaded cells is a key athero-protective event that counteracts cholesterol uptake. The imbalance between cholesterol efflux and uptake determines the prevention or development of atherosclerosis. Many proteins and factors participate in the cholesterol efflux event. However, there are currently no systematic models of reverse cholesterol transport (RCT) that include most RCT-related factors and events. On the basis of recent research findings from other and our laboratories, we propose a novel model of one center and four systems with coupling transportation and networking regulation. This model represents a common way of cholesterol efflux; however, the systems in the model consist of different proteins/factors in different cells. In this review, we evaluate the novel model in vascular smooth muscle cells (VSMCs) and macrophages, which are the most important original cells of foam cells. This novel model consists of 1) a caveolae transport center, 2) an intracellular trafficking system of the caveolin-1 complex, 3) a transmembrane transport system of the ABC-A1 complex, 4) a transmembrane transport system of the SR-B1 complex, and 5) an extracelluar trafficking system of HDL/Apo-A1. In brief, the caveolin-1 system transports cholesterol from intracellular compartments to caveolae. Subsequently, both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to extracellular HDL/Apo-A1. The four systems are linked by a regulatory network. This model provides a simple and concise way to understand the dynamic process of atherosclerosis.
摘要：
Aim: High density lipoprotein (HDL) and its apolipoproteins can promote cholesterol efflux from macrophage foam cells via the ATP-binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor class B type. (SR-BI). Liver X receptors (LXRs) operate as cholesterol sensors which may protect from cholesterol overload by stimulating cholesterol efflux from cells to HDL through ABCA1, ABCG1 and SR-BI. The regulation of ABCA1, ABCG1 and SR-BI expression by cytokines present within the microenvironment of the atheroma may play an important role in determining the impact of reverse cholesterol transport on the atherosclerotic lesion. In the current study, we examined the effect of transforming growth factor-alpha 1 (TGF-alpha 1) on expressions of ABCA1, ABCG1 and SR-BI and explored the role of LXR alpha in the regulation of ABCA1, ABCG1 and SR-BI in THP-1 macrophage-derived foam cells. Methods and Results: TGF-alpha 1 significantly increased expressions of ABCA1, ABCG1 and SR-BI at both transcriptional and translational levels in a dose-dependent and time-dependent manner. Cellular cholesterol content was decreased while cholesterol efflux was increased by TGF-alpha 1 treatment. Moreover, LXR alpha was up-regulated by TGF-alpha 1 treatment. In addition, LXR alpha small interfering RNA completely abolished the promotion effect induced by TGF-alpha 1. Conclusion: These results provide evidence that TGF-alpha 1 up-regulates expressions of ABCA1, ABCG1 and SR-BI through the LXR alpha pathway in THP-1 macrophage-derived foam cells.
作者机构：
[Zhu Bing-Yang; Luo Di-Xian; Xu Can-Xin; Wang Chun; Gao Zhi-Ping; Liao Duan-Fang] Univ S China, Life Sci Res Ctr, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Liao Duan-Fang] Hunan Univ Chinese Med, Dept Tradit Chinese Diagnost, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Liao Duan-Fang] U;Univ S China, Life Sci Res Ctr, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
通讯机构：
[Yin, Weidong] U;Univ S China, Life Sci Res Ctr, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
摘要：
Insulin resistance and dyslipidemia are both considered to be risk factors for metabolic syndrome. Low levels of IGF1 are associated with insulin resistance. Elevation of low-density lipoprotein cholesterol (LDL-C) concomitant with depression of high-density lipoprotein cholesterol (HDL-C) increase the risk of obesity and type 2 diabetes mellitus (T2DM). Liver secretes IGF1 and catabolizes cholesterol regulated by the rate-limiting enzyme of bile acid synthesis from cholesterol 7 alpha-hydroxylase (CYP7A1). NO-1886, a chemically synthesized lipoprotein lipase activator, suppresses diet-induced insulin resistance with the improvement of HDL-C. The goal of the present study is to evaluate whether NO-1886 upregulates IGF1 and CYP7A1 to benefit glucose and cholesterol metabolism. By using human hepatoma cell lines (HepG2 cells) as an in vitro model, we found that NO-1886 promoted IGF1 secretion and CYP7A1 expression through the activation of signal transducer and activator of transcription 5 (STAT5). Pretreatment of cells with AG 490, the inhibitor of STAT pathway, completely abolished NO1886-induced IGF1 secretion and CYP7A1 expression. Studies performed in Chinese Bama minipigs pointed out an augmentation of plasma IGF1 elicited by a single dose administration of NO-1886. Long-term supplementation with NO-1886 recovered hyperinsulinemia and low plasma levels of IGF1 suppressed LDL-C and facilitated reverse cholesterol transport by decreasing hepatic cholesterol accumulation through increasing CYP7A1 expression in high-fat/high-sucrose/high-cholesterol diet minipigs. These findings indicate that NO-1886 upregulates IGF1 secretion and CYP7A1 expression to improve insulin resistance and hepatic cholesterol accumulation, which may represent an alternative therapeutic avenue of NO-1886 for T2DM and metabolic syndrome. Journal of Endocrinology (2010) 204, 47-56
作者机构：
[He Ji-Shan; Xiong Ping; Guo Ping] Cent S Univ, Sch Infophys & Geomat Engn, Changsha 410083, Peoples R China.;[Li Xin-Xia; Guo Ping] Univ S China, Dept Nucl Phys, Hengyang 421001, Peoples R China.
通讯机构：
[Guo Ping] C;Cent S Univ, Sch Infophys & Geomat Engn, Changsha 410083, Peoples R China.
关键词：
field emission;molybdenum dioxide;enhancement factor
摘要：
The transport and capture of therapeutic magnetic nanoparticles in human microvasculature is studied numerically. The nanoparticles are injected into a vascular system upstream from malignant tissue, and are captured at the tumour site with the aid of a local applied magnetic field positioned outside the body. Taking into account the dominant magnetic and fluidic forces on the particles, our study shows that the nanoparticles can be directed to and concentrated at the desired zone that is within a few centimetres from the surface of the body. In addition, influence of the particles size, average blood flow velocity and the diameter of the blood vessel on the captured efficiency are parametrically analysed.
期刊：
Abstract and Applied Analysis,2009年2009:1-12 ISSN：1085-3375
通讯作者：
Ouyang, ZG
作者机构：
[Ouyang, Zigen; Zhong, Jichao; Zou, Shuliang] Univ S China, Ctr Nucl Energy Econ & Management, Hengyang 421001, Peoples R China.;[Ouyang, Zigen; Zhong, Jichao] Univ S China, Sch Phys & Mat, Hengyang 421001, Peoples R China.
通讯机构：
[Ouyang, ZG ] ;Univ S China, Ctr Nucl Energy Econ & Management, Hengyang 421001, Peoples R China.
关键词：
A class of second-order nonlinear differential equations with damping term (r(t)|x′(t)|σ−1x′(t))′+p(t)|x′(t)|σ−1x′(t)+q(t)f(x(t))=0 are investigated in this paper. By using a new method;we obtain some new sufficient conditions forthe oscillation of the above equation;and some references are extended in this paper. Examples areinserted to illustrate this result. Published: 2009 First available in Project Euclid: 16 March 2010 zbMATH: 1181.34044 MathSciNet: MR2559281 Digital Object Identifier: 10.1155/2009/897058
摘要：
A class of second-order nonlinear differential equations with damping term (r(t) | x ′ (t) | -1 x ′ (t)) ′ +p(t) | x ′ (t) | -1 x ′ (t)+q(t)f(x(t))=0 are investigated in this paper. By using a new method, we obtain some new sufficient conditions for the oscillation of the above equation, and some references are extended in this paper. Examples are inserted to illustrate this result.
作者机构：
[Tang, Chao-ke; Li, Xiao-xu; Hu, Yan-wei; Liu, Xie-hong; Cao, Dong-li; Hao, Xin-rui; Xiao, Ji] Nanhua Univ, Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov,Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.;[Liao, Duan-fang] Univ S China, Inst Pharm & Pharmacol, Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.;[Xiang, Jim] Univ Saskatchewan, Dept Oncol, Res Unit, Hlth Res Div,Saskatchewan Canc Agcy, Saskatoon, SK S7N 4H4, Canada.
通讯机构：
[Tang, Chao-ke] N;Nanhua Univ, Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov,Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.
关键词：
ATP-binding cassette transporter A1;IFN-gamma;JAK/STAT1;Atherosclerosis;Reverse cholesterol transport
摘要：
Interferon gamma (IFN-gamma) is an immunomodulatory and anti-microbial cytokine, which has a variety of proatherogenic effects. It has been reported that IFN-gamma can down-regulate ABCA1 expression. However, its mechanism is elusive. In the present Study, we have investigated the effect of IFN-gamma on ABCA1 expression and cholesterol efflux in THP-1 macrophage-derived foam cells. IFN-gamma decreased ABCA1 expression at both transcriptional and translational levels in a dose-dependent manner. Cellular cholesterol content was increased while cholesterol efflux was decreased by IFN-gamma treatment. Liver X receptor a (LXR alpha), which can regulate the expression of ABCA1, was also down-regulated by IFN-gamma treatment. LXR alpha-specific activation by LXR alpha agonist almost compensated the down-regulation of ABCA1 expression by IFN-gamma, while siRNA of LXR alpha led to down-regulation of ABCA1 expression more significantly than IFN-gamma, IFN-gamma induced phosphorylation of STAT1 and expression of STAT1 alpha a in the nucleus, which was inhibited by a JAK inhibitor AG-490. Treatment with STAT1 siRNA further enhanced down-regulation of LXR alpha mRNA by IFN-gamma. Furthermore, AG-490 and STAT1 siRNA almost compensated the effect of IFN-gamma on ABCA1 expression and cholesterol efflux. In conclusion, IFN-gamma may first down-regulate expression of LXR alpha through the JAK/STAT1 signaling pathway and then decrease expression of ABCA1 and cholesterol efflux in THP-1 macrophage-derived foam cells. Therefore, our study may be useful in understanding the critical effect of IFN-gamma in pathogenesis of atherosclerosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
