作者机构：
[Tang, Chao-Ke; Yu, Xiao-Hua] Univ South China, Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.;[Tang, Chao-Ke; Yin, Kai] Univ South China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.;[Fu, Yu-Chang] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.;[Zhang, Da-Wei] Univ Alberta, Dept Pediat, Edmonton, AB T6G 2S2, Canada.;[Zhang, Da-Wei] Univ Alberta, Grp Mol & Cell Biol Lipids, Edmonton, AB T6G 2S2, Canada.
通讯机构：
[Yin, Kai] Univ South China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.
关键词：
ABCA1;ABCG1;ACAT1;AGE;ATP-binding cassette transporter A1;ATP-binding cassette transporter G1;Atherosclerosis;CD36;CE;ERK1/2;FC;Foam cells;HDL;LDLR;LXR;MAPK;PI3K;PKB;PKC;PPAR response elements;PPAR-gamma;PPREs;RCT;RXR;SR-A;SR-BI;TGF-beta;acyl coenzyme A:cholesterol acyltransferase-1;advanced glycation end products;apoA-I;apoE;apolipoprotein A-I;apolipoprotein E;cholesterol ester;extracellular signal-regulated kinases 1 and 2;free cholesterol;high-density lipoprotein;liver X receptor;low-density lipoprotein receptor;mitogen-activated protein kinase;nCEH;neutral cholesteryl ester hydrolase;ox-LDL;oxidized low-density lipoprotein;peroxisome proliferator-activated receptor-gamma;phosphatidylinositol 3-kinase;protein kinase B;protein kinase C;retinoid X receptor;reverse cholesterol transport;scavenger receptor BI;scavenger receptor class A;transforming growth factor-beta
摘要：
Atherosclerosis is a chronic disease characterized by the deposition of excessive cholesterol in the arterial intima. Macrophage foam cells play a critical role in the occurrence and development of atherosclerosis. The generation of these cells is associated with imbalance of cholesterol influx, esterification and efflux. CD36 and scavenger receptor class A (SR-A) are mainly responsible for uptake of lipoprotein-derived cholesterol by macrophages. Acyl coenzyme A:cholesterol acyltransferase-1 (ACAT1) and neutral cholesteryl ester hydrolase (nCEH) regulate cholesterol esterification. ATP-binding cassette transporters A1 (ABCA1), ABCG1 and scavenger receptor BI (SR-BI) play crucial roles in macrophage cholesterol export When inflow and esterification of cholesterol increase and/or its outflow decrease, the macrophages are ultimately transformed into lipid-laden foam cells, the prototypical cells in the atherosclerotic plague. The aim of this review is to describe what is known about the mechanisms of cholesterol uptake, esterification and release in macrophages. An increased understanding of the process of macrophage foam cell formation will help to develop novel therapeutic interventions for atherosclerosis. (c) 2013 The Authors. Published by Elsevier B.V. All rights reserved.
期刊：
Molecular Medicine Reports,2012年5(3):753-760 ISSN：1791-2997
通讯作者：
Wang, Xiaochun
作者机构：
[Zhou, Feng; Liu, Lipeng; Tian, Zhi; Su, Min; Huang, Chunxia; Liu, Meiling; Guo, Xiaofang; Long, Yu] Changsha Med Univ, Dept Biochem & Mol Biol, Changsha 410219, Hunan, Peoples R China.;[Wang, Xiaochun] Cent S Univ, Dept Med Lab Examinat, Changsha 410013, Hunan, Peoples R China.;[Yu, Xiaohua] Nanhua Univ, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Wu, Xinhua] Cent S Univ, Xiangya Hosp, Dept Obstet & Gynecol, Changsha 410078, Hunan, Peoples R China.
通讯机构：
[Wang, Xiaochun] Cent S Univ, Dept Med Lab Examinat, Changsha 410013, Hunan, Peoples R China.
关键词：
Apoptosis;Bcl-2;HeLa;MiR-143;Proliferation
摘要：
microRNAs (miRNAs) are small non-coding RNA molecules of 21-24 nt that regulate the expression of other genes by transcriptional inhibition or translational repression. Multiple lines of evidence suggest that miRNAs play important roles in tumor development and progression. We identified 24 mi RNAs markedly and aberrantly expressed in human cervical cancer. The most significantly deregulated was miR-143 as determined by miRNA microarray analysis. miR-143 was introduced into He La cells and it was found that the overexpression of miR-143 significantly inhibited He La cell proliferation and promoted apoptosis; anti-miR-143 rescued the effects. He La cells transfected with pre-miR-143, pre-anti-miR-143 or control mi RNA precursor were injected subcutaneously into the flanks of female athymic nude mice, and the overexpression of miR-143 suppressed the formation of tumors. Compared with normal cervical tissues, the levels of Bcl-2 were increased in miR-143-downregulated tissues. Sustained overexpression of miR-143 in He La cells resulted in suppression of Bcl-2 expression, and knockdown of miR-143 by anti-miR-143 increased Bcl-2 expression. In addition, overexpression of Bcl-2 partially reversed the inhibition of proliferation and promotion of apoptosis in the He La cells caused by miR-143. Furthermore, miR-143 suppressed the activity of a luciferase reporter carrying the 3'-UTR of Bcl-2, which was abolished by mutation of the predicted miR-143-binding site, indicating that Bcl-2 is a miR-143 target gene. Our study revealed a molecular link between miR-143 and Bcl-2. Direct involvement in the regulation of Bcl-2 may be one of the mechanisms through which mi R-143 may play a role in the pathogenesis of cervical cancer.
摘要：
Rationale: Macrophage cholesterol homeostasis maintenance is the result of a balance between influx, endogenous synthesis, esterification/hydrolysis and efflux. Excessive accumulation of cholesterol leads to foam cell formation, which is the major pathology of atherosclerosis. Previous studies have shown that miR-27 (miR-27a and miR-27b) may play a key role in the progression of atherosclerosis. Objective: We set out to investigate the molecular mechanisms of miR-27a/b in intracellular cholesterol homeostasis. Methods and results: In the present study, our results have shown that the miR-27 family is highly conserved during evolution, present in mammals and directly targets the 3' UTR of ABCA1, LPL, and ACAT1. apoA1, ABCG1 and SR-B1 lacking miR-27 bind sites should not be influenced by miR-27 directly. miR-27a and miR-27b directly regulated the expression of endogenous ABCA1 in different cells. Treatment with miR-27a and miR-27b mimics reduced apoA1-mediated cholesterol efflux by 33.08% and 44.61% in THP-1 cells, respectively. miR-27a/b also regulated HDL-mediated cholesterol efflux in THP-1 macrophages and affected the expression of apoA1 in HepG2 cells. However, miR-27a/b had no effect on total cellular cholesterol accumulation, but regulated the levels of cellular free cholesterol and cholesterol ester. We further found that miR-27a/b regulated the expression of LPL and CD36, and then affected the ability of THP-1 macrophages to uptake Dil-oxLDL. Finally, we identified that miR-27a/b regulated cholesterol ester formation by targeting ACAT1 in THP-1 macrophages. Conclusion: These findings indicate that miR-27a/b affects the efflux, influx, esterification and hydrolysis of cellular cholesterol by regulating the expression of ABCA1, apoA1, LPL, CD36 and ACAT1. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
作者机构：
[Tang, Chao-ke; Yin, Kai] Univ S China, Inst Cardiovasc Res, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Liao, Duan-fang] Hunan Univ Chinese Med, Sch Pharm, Dept Tradit Chinese Diagnost, Changsha, Hunan, Peoples R China.
通讯机构：
[Tang, Chao-ke] Univ S China, Inst Cardiovasc Res, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
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)-gamma and interleukin (IL)-1 beta have been shown to inhibit the expression of ABCA1, while antiatherogenic cytokines, including IL-10 and transforming growth factor (TGF)-beta 1, have been shown to promote the expression of ABCA1 Moreover, some cytokines such as tumor necrosis factor (TNF)-alpha 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 ROT. 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. (C) 2010 The Feinstein Institute for Medical Research, www.feinsteininstitute.org
期刊：
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer,2013年1836(2):197-210 ISSN：0304-419X
通讯作者：
Feng, Shaolong
作者机构：
[Feng, Shaolong] Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.;[Cao, Zhaohui] Univ South China, Sch Pharm & Life Sci, Hengyang 421001, Peoples R China.;[Wang, Xinming] Chinese Acad Sci, Guangzhou Inst Geochem, State Key Lab Organ Geochem, Guangzhou 510640, Guangdong, Peoples R China.
通讯机构：
[Feng, Shaolong] Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.
关键词：
Aryl hydrocarbon receptor (AHR);Cancer
摘要：
Aryl hydrocarbon receptor (AHR), a cytosolic ligand-activated transcription factor, belongs to the member of bHLH/PAS family of heterodimeric transcriptional regulators and is widely expressed in a variety of animal species and humans. Recent animal and human data suggested that AHR is involved in various signaling pathways critical to cell normal homeostasis, which covers multiple aspects of physiology, such as cell proliferation and differentiation, gene regulation, cell motility and migration, inflammation and others. Dysregulation of these physiological processes is known to contribute to events such as tumor initiation, promotion, and progression. Increasing epidemiological and experimental animal data provided substantial support for an association between abnormal AHR function and cancer, implicating AHR may be a novel drug-interfering target for cancers. The proposed underlying mechanisms of its actions in cancer involved multiple aspects, (a) inhibiting the functional expression of the key anti-oncogenes (such as p53 and BRCA1), (b) promoting stem cells transforming and angiogenesis, (c) altering cell survival, proliferation and differentiation by influencing the physiologic processes of cell-cycle, apoptosis, cell contact-inhibition, metabolism and remodel of extracellular matrix, and cell-matrix interaction, (d) cross-talking with the signaling pathways of estrogen receptor and inflammation. This review aims to provide a brief overview of recent investigations into the role of AHR and the underlying mechanisms of its actions in cancer, which were explored by the new technologies emerging in recent years. (C) 2013 Elsevier B.V. All rights reserved.
摘要：
Rationale: Macrophage accumulation of cholesterol leads to foam cell formation which is a major pathological event of atherosclerosis. Recent studies have shown that microRNA (miR)-19b might play an important role in cholesterol metabolism and atherosclerotic diseases. Here, we have identified miR-19b binding to the 3'UTR of ATP-binding cassette transporter A1 (ABCA1) transporters, and further determined the potential roles of this novel interaction in atherogenesis. Objective: To investigate the molecular mechanisms involved in a miR-19b promotion of macrophage cholesterol accumulation and the development of aortic atherosclerosis. Methods and results: We performed bioinformatics analysis using online websites, and found that miR-19b was highly conserved during evolution and directly bound to ABCA1 mRNA with very low binding free energy. Luciferase reporter assay confirmed that miR-19b bound to 3110-3116 sites within ABCA1 3'UTR. MiR-19b directly regulated the expression levels of endogenous ABCA1 in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by qRT-PCR and western blot. Cholesterol transport assays revealed that miR-19b dramatically suppressed apolipoprotein AI-mediated ABCA1-dependent cholesterol efflux, resulting in the increased levels of total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) as revealed by HPLC. The excretion of H-3-cholesterol originating from cholesterol-laden MPMs into feces was decreased in mice overexpressing miR-19b. Finally, we evaluated the proatherosclerotic role of miR-19b in apolipoprotein E deficient (apoE(-/-)) mice. Treatment with miR-19b precursor reduced plasma high-density lipoprotein (HDL) levels, but increased plasma low-density lipoprotein (LDL) levels. Consistently, miR-19b precursor treatment increased aortic plaque size and lipid content, but reduced collagen content and ABCA1 expression. In contrast, treatment with the inhibitory miR-19b antisense oligonucleotides (ASO) prevented or reversed these effects. Conclusion: MiR-19b promotes macrophage cholesterol accumulation, foam cell formation and aortic atherosclerotic development by targeting ABCA1. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
摘要：
Vascular smooth muscle cells (VSMCs) were prepared from thoracic aortas of male Sprague–Dawley rats by the explant method to observe VSMC proliferation via phosphoinositide 3 kinase (PI3K)/Akt signaling transduction pathway induced by apelin-13. Expression of PI3K, phospho-PI3K, phospho-Akt, ERK1/2, phospho-ERK1/2 and cyclin D1 was detected by western blot analysis. Results showed that apelin-13 promoted the expression of phospho-PI3K and phospho-Akt in dose- and time-dependent manner. PI3K inhibitor LY294002 significantly decreased the expression of phospho-PI3K, phospho-Akt, phospho-ERK1/2, and cyclin D1 induced by apelin-13. The Akt inhibitor 1701-1 significantly diminished the expression of phospho-Akt, phospho-ERK1/2, and cyclin D1 stimulated by apelin-13. MTT assay results showed that PI3K inhibitor LY294002 and Akt inhibitor 1701-1 significantly inhibited the VSMC proliferation induced by apelin-13. Apelin-13 promoted VSMC proliferation through PI3K/Akt signaling transduction pathway.
摘要：
Evidences indicate that a complex relationship exists among sleep disorders, obesity and insulin resistance. NEU-P11 is a novel melatonin agonist used in treatment of psychophysiological insomnia, and in animal studies NEU-P11 showed sleep-promoting effect. In this study, we applied NEU-P11 on obese rats to assess its potential melatoninergic effects in vivo. Obese models were established using high-fat/high-sucrose-fed for 5 months. NEU-P11 (10 mg/kg)/melatonin (4 mg/kg)/vehicle were administered by a daily intraperitoneal injection respectively for 8 weeks. Our results showed that NEU-P11 or melatonin inhibited both body weight gain and deposit of abdominal fat with no influence on food intake. The impaired insulin sensitivity and antioxidative potency were improved and the levels of plasma glucose, total cholesterol (TC), triglycerides (TG) decreased with an increased in HDL-cholesterol (HDL-c) after NEU-P11 or melatonin administration. These data suggest that NEU-P11, like melatonin, decreased body weight gain and improved insulin sensitivity and metabolic profiles in obese rats. We conclude that NEU-P11 has a melatoninergic effect on regulating body weight in obese rats and also improving metabolic profiles and efficiently enhancing insulin sensitivity. (C) 2009 Elsevier Ltd. All rights reserved.
期刊：
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society,2010年58(6):517-527 ISSN：0022-1554
通讯作者：
Chen, Zhuchu
作者机构：
[Li, Maoyu; Xiao, Zhiqiang; Li, Cui; Li, Feng; Peng, Fang; Xiao, Zhefeng; Chen, Zhuchu; Li, Guoqing] Cent S Univ, Xiangya Hosp, Key Lab Canc Prote, Chinese Minist Hlth, Changsha 410008, Hunan, Peoples R China.;[Yu, Yanhui; Li, Feng; Ouyang, Yongmei; Xiao, Zhefeng] Cent S Univ, Canc Res Inst, Xiangya Sch Med, Changsha 410008, Hunan, Peoples R China.;[Li, Guoqing] Univ S China, Sch Pharm & Life Sci, Dept Biol, Hengyang, Hunan, Peoples R China.;[Chen, Yongheng] Univ So Calif, Los Angeles, CA USA.;[Chen, Zhuchu] Cent S Univ, Xiangya Hosp, Key Lab Canc Prote, Chinese Minist Hlth, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China.
通讯机构：
[Chen, Zhuchu] Cent S Univ, Xiangya Hosp, Key Lab Canc Prote, Chinese Minist Hlth, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China.
关键词：
NPC;FFPE;iTRAQ;2D LC-MS/MS
摘要：
Formalin-fixed, paraffin-embedded (FFPE) tissue specimens represent a potentially valuable resource for protein biomarker investigations. In this study, proteins were extracted by a heat-induced antigen retrieval technique combined with a retrieval solution containing 2% SDS from FFPE tissues of normal nasopharyngeal epithelial tissues (NNET) and three histological types of nasopharyngeal carcinoma (NPC) with diverse differentiation degrees. Then two-dimensional liquid chromatography-tandem mass spectrometry coupled with isobaric tags for relative and absolute quantification (iTRAQ) labeling was employed to quantitatively identify the differentially expressed proteins among the types of NPC FFPE tissues. Our study resulted in the identification of 730 unique proteins, the distributions of subcellular localizations and molecular functions of which were similar to those of the proteomic database of human NPC and NNET that we had set up based on the frozen tissues. Additionally, the relative expression levels of cathepsin D, keratin8, SFN, and stathmin1 identified and quantified in this report were consistent with the immunohistochemistry results acquired in our previous study. In conclusion, we have developed an effective approach to identifying protein changes in FFPE NPC tissues utilizing iTRAQ technology in conjunction with an economical and easily accessible sample preparation method. (J Histochem Cytochem 58:517-527, 2010)
摘要：
Atherosclerosis (As) is now widely appreciated to represent a chronic inflammatory reaction of the vascular wall in response to dyslipidemia and endothelial distress involving the inflammatory recruitment of leukocytes and the activation of resident vascular cells. MicroRNAs (miRNAs) are a group of endogenous, small (similar to 22 nucleotides in length) non-coding RNA molecules, which function specifically by base pairing with mRNA of genes, thereby induce translation repressions of the genes within metazoan cells. Recently, the function of miR-27, one of the miRNAs, in the initiation and progression of atherosclerosis has been identified. In vivo and in vitro studies suggest that miR-27 may serve as a diagnostic and prognostic marker for atherosclerosis. More recently, studies have identified important roles for miR-27 in angiogenesis, adipogenesis, inflammation, lipid metabolism, oxidative stress, insulin resistance and type 2 diabetes, etc. In this review, we focus on the role of miR-27 in the development of vulnerable atherosclerotic plaques, potential as a disease biomarker and novel therapeutic target in atherosclerosis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
摘要：
Cholesterol is essential for the growth and function of all mammalian cells, but abnormally increased blood cholesterol is a major risk factor for atherosclerotic cardiovascular disease. ATP-binding cassette (ABC) transporters G5 (ABCG5) and G8 (ABCG8) form an obligate heterodimer that limits intestinal absorption and facilitates biliary secretion of cholesterol and phytosterols. Consistent with their function, ABCG5 and ABCG8 are located on the apical membrane of enterocytes and hepatocytes. Liver X receptor is the major positive regulator of ABCG5 and ABCG8 expression. Mutations in either of the two genes cause sitosterolemia, a condition in which cholesterol and plant sterols accumulate in the circulation leading to premature cardiovascular disease. Overexpression of ABCG5 and ABCG8 in mice retards diet-induced atherosclerosis because of reduced circulating and hepatic cholesterol. In the current review, we summarize recent developments and propose a future framework that provides new perspectives on the regulation of cholesterol metabolism and treatment of atherosclerotic cardiovascular disease.
作者：
Ling, H. -y.;Hu, B.;Hu, X. -b.;Zhong, J.;Feng, S. -d.;Qin, L.;Liu, G.;Wen, G. -b.;Liao, D. -f.*
期刊：
Experimental and Clinical Endocrinology & Diabetes,2012年120(9):553-559 ISSN：0947-7349
通讯作者：
Liao, D. -f.
作者机构：
[Ling, H. -y.; Hu, B.] Univ S China, Sch Med, Dept Physiol, Hengyang, Peoples R China.;[Liao, D. -f.] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha 410208, Hunan, Peoples R China.;[Ling, H. -y.] Univ S China, Ctr Basic Med Postdoctoral Studies, Hengyang, Peoples R China.;[Hu, X. -b.] Univ S China, Sch Life Sci & Technol, Dept Biochem & Mol Biol, Hengyang, Peoples R China.;[Wen, G. -b.; Zhong, J.] Univ S China, Affiliated Hosp 1, Inst Clin Res, Hengyang, Peoples R China.
通讯机构：
[Liao, D. -f.] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha 410208, Hunan, Peoples R China.
