作者机构：
[Tian Hai-Hong; Liu Yan-Mei; Deng Shui-Xiu; Chen Lin-Xi; Qin Xu-Ping; Chen Yun] Univ South China, Inst Pharm & Pharmacol, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Dai Zhong] Guangdong Med Coll, Dept Pharmacol, Dongguan 523808, Peoples R China.;[Wang H Donna] Michigan State Univ, Dept Med, E Lansing, MI 48824 USA.
通讯机构：
[Qin Xu-Ping] U;Univ South China, Inst Pharm & Pharmacol, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Peoples R China.
摘要：
Caveolae and caveolin-1 participate in the transportation of cholesterol and cell signal transduction. Our previous studies showed that the inhibitory effect of calcitonin gene-related peptide (CGRP) on the vascular smooth muscle cells (VSMCs) was related to decreasing the activity of extracellular signal-regulated kinase (ERK)_(1/2) and increasing the expression of caveolin-1. In the present study, we investigated the role of caveolae and caveolin-1 in proliferation of VSMCs and whether there are interaction between the caveolin-1 and ERK_(1/2) in the inhibitory effect of CGRP signal pathway. VSMCs were prepared from thoracic aorta of male Sprague-Dawley rat by the classic explants method, the passage 3 ~ 10 VSMCs were used for the present study. 10% fetal bovine serum (FBS) was employed as a stimulus for the proliferation of VSMCs. β-Cyclodextrin or filipin was used to deplete cholesterol in the caveolae. Proliferation of VSMCs was estimated by methylthiazoletrazolium (MTT) assay and Flow Cytometry. Western blotting and co-immunoprecipitation were used to determine interaction of p-ERK_(1/2) or caveolin-1. Results showed that CGRP significantly inhibited VSMC proliferation and down-regulated phosphorylation of ERK_(1/2). Incubation of VSMCs with β-cyclodextrin or filipin promoted cells proliferation, up-regulated phosphorylation of ERK_(1/2), attenuated the inhibitory action of CGRP on VSMC proliferation and decreased caveolin-1 expression. Pretreatment with CGRP increased the direct binding of cavolin-1 with phosphorylated(p-) ERK_(1/2) but not non-phosphorylated ERK_(1/2) in the presence of 10%FBS. Our results revealed that caveolae and caveolin-1 may contribute to the inhibitory effect of CGRP on the VSMC proliferation, and the mechanism may be related to the deceased nuclei translocation of p-ERK_(1/2) because of the increased binding of caveolin-1 with p-ERK_(1/2).
摘要：
Apelin is a bioactive peptide discovered recently that has been proved to be an endogenous ligand of the APJ receptor. Apelin and APJ are widely distributed in the central nervous system and peripheral tissues. Researches have confirmed that apelin/APJ involved in a wide range of physiological and pathological functions in the cardiovascular system. Investigations indicated that apelin is a novel critical factor in the development of atherosclerosis (AS). In this review, we discuss the roles of apelin in the vascular smooth muscle cell proliferation, monocytes-endothelial cell adhesion, and angiogenesis that potentially reveals a new cellular mechanism of AS. Considering these roles, apelin and APJ may be novel therapeutic targets of AS.
作者机构：
[唐江琼; 陈临溪; 秦旭平; 秦又发; 郑元斌] Institute of Pharmacology and Pharmacy, University of South China, Hengyang 421001, China;Department of Pharmacology, Kunming General Hospital of Chendu Military Command, Kunming 650032, China;[孙飞] Institute of Pharmacology and Pharmacy, University of South China, Hengyang 421001, China, Department of Pharmacology, Kunming General Hospital of Chendu Military Command, Kunming 650032, China
通讯机构：
[Qin, X.-P.] I;Institute of Pharmacology and Pharmacy, University of South China, China
作者机构：
[She, M.-H.; Jiang, W.-Y.; Hu, X.-B.; Yin, W.-D.] Dept. of Biochemistry and Molecular Biology, School of Life Sciences and Technology, University of South China, Hengyang Hunan 421001, China;[Yang, S.-H.] First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China;[Laudon, M.] Drug Discovery, Neurim Pharmaceuticals Lad, Tel-Aviv, Israel
作者机构：
[Wang, P.-P.] Institute of Cardiovascular Diseases, University of South China, Hengyang Hunan 421001, China;[She, M.-H.] Dept. of Biochemistry and Molecular Biology, University of South China, Hengyang Hunan 421001, China;[Laudon, M.] Neurim Pharmaceuticals Ltd., Israel;[Yin, W.-D.] Institute of Cardiovascular Diseases, University of South China, Hengyang Hunan 421001, China, Dept. of Biochemistry and Molecular Biology, University of South China, Hengyang Hunan 421001, China
关键词：
胰岛素抵抗;甘油三酯;脂肪组织甘油三酯酶;激素敏感性脂肪酶
摘要：
目的探讨脂肪组织甘油三酯酶(adipose triglyceride lipase,ATGL)及激素敏感性脂肪酶(hormone-sensitive lipase,HSL)在褪黑素非选择性受体激动剂Neu-p11改善高糖高胰岛素(high glucose and insulin,HGI)诱导的3T3-L1脂肪细胞胰岛素抵抗(insulin resistance,IR)中的作用及机制.方法培养3T3-L1脂肪细胞,HGI诱导IR模型.以葡萄糖消耗量及细胞内甘油三酯(triglyceride,TG)定量测定作为检测指标,Western blot检测蛋白水平的表达情况.结果HGI孵育减少脂肪细胞葡萄糖摄取,促进细胞内TG积聚,同时伴有ATGL及HSL的蛋白表达下调.Neu-p11干预逆转了HGI对脂肪细胞的作用效应,而MT2竞争性拮抗剂luzindole却拮抗了Neu-p11的上述效应.结论Neu-p11以MT2受体依赖性方式抑制IR脂肪细胞TG沉积,可能与其上调ATGL、HSL蛋白的表达,促进TG水解相关.
作者机构：
[Cao, Jiangang; Chen, Linxi; Lv, Deguan; Lu, Qixuan] Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China
通讯机构：
[Linxi Chen *] I;Institute of Pharmacy and Pharmacology , University of South China , Hengyang 421001 , China
关键词：
Unanticipated;miRNA;apelin
摘要：
Recently, a paper by Kim et al [1] in Nature Medicine magazine in January, 2013 showed that apelin (also known as APLN) inhibits fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) expression to ameliorate pulmonary hypertension by regulating the expression of miR-424 and miR-503. This study revealed the molecular mechanism of apelin in inhibiting the process of pulmonary arterial hypertension (PAH) and discovered the role of apelin in regulating miRNA generation for the first time. miRNA functions in the transcriptional regulation of gene expression to control cellular processes. miRNA is a key regulatory factor of protein expression, but the generation and regulation mechanism of miRNA is still unclear. These novel findings bring us inspiration for further research, especially on the mechanism of miRNA generation. Experiments on revealing endogenous active substance, which regulates the generation of miRNAs or revealing miRNAs that regulate the expression of apelin, may bring more breakthroughs in the future.
作者机构：
[Wang Chang-Bo; Li Bin-Yuan; Qin Ling-Xue; Dong Xiao; He Shu-Ya; Wang San-Hu; Ma Yun] Univ South China, Dept Biol & Biochem, Hengyang 421001, Peoples R China.;[Xu Can] Univ South China, Affiliated Hosp 1, Dept Cardiol, Hengyang 421001, Peoples R China.
通讯机构：
[He Shu-Ya] U;Univ South China, Dept Biol & Biochem, Hengyang 421001, Peoples R China.
关键词：
FXR1P;CMAS;GM1;biological effect;PC12;VSMC
摘要：
Fragile X syndrome (FXS) is a genetic mental retardation disease, with incidence second only to trisomy 21 syndrome. Fragile X mental retardation protein(FMRP), is the causative factor of FXS and encoded by the Fragile X mental retardation1(FMR1)gene, which is widely expressed in cells of the nerve, muscle, and testes. Fragile X related protein 1 (FXR1P) is encoded by a homologous gene to FMR1——Fragile X related gene 1 (FXR1) and can interact with proteins and RNAs. Many illnesses were involved in the altered expression of FXR1. To understand the biological effect of the interaction between FXR1P and CMAS, we constructed a FXR1 overexpression vector and investigated its expression in PC12 (the rat pheochromocytoma) cells and VSMC (vascular smooth muscle cell) and the effect of the overexpression on cell morphology and several cell processes related to CMP-N-acetylneuraminic acid synthetase (CMAS) activity. We demonstrate that the overexpression of FXR1 gene can increase activity of CMAS in PC12 cells and provide a certain degree growth protection for that cells. Thus, it suggests FXR1P is a tissue-specific regulator to alter the concentration of GM1 in PC12 cells, but not in VSMC.
作者机构：
[Li, Lifang] Univ South China, Dept Microbiol & Immunol, Hengyang 421001, Peoples R China.;[Xie, Feng; Guo, Yu; Li, Lanfang; Lv, Deguan; Lu, Qixuan; Tang, Guotao; Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.;[Zhang, Zidong] Univ Mississippi, Med Ctr, Dept Microbiol, Jackson, MS 39216 USA.;[Li, Jian] Beijing Hosp, Key Lab Geriatr, Beijing 100730, Peoples R China.;[Li, Jian] Minist Hlth, Beijing Inst Geriatr, Beijing 100730, Peoples R China.
通讯机构：
[Chen, Linxi] U;Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
关键词：
G protein-coupled receptor;cell proliferation;vascular smooth muscle cell;Jagged-1/Notch3
摘要：
The apelin/apelin receptor (APJ, apelin–angiotensin receptor-like 1) system is a newly deorphanized G protein-coupled receptor system. Both apelin and APJ that are important regulatory factors are expressed in the cardiovascular system. Our previous studies demonstrated that apelin-13 significantly stimulated vascular smooth muscle cell (VSMC) proliferation. In this paper, our data suggested that the Jagged-1/Notch3 signaling transduction pathway is involved in apelin-13-induced VSMC proliferation by promoting the expression of Cyclin D1. Results indicated that apelin-13 stimulates the proliferation of VSMC and the expression of Jagged-1 and Notch3 in concentration- and time-dependent manners. The increased expression of Jagged-1 and Notch3 induced by apelin-13 could be abolished by extracellular signal-regulated protein kinase (ERK) blockade. PD98059 (ERK inhibitor) can inhibit the activation of Jagged-1/Notch3 induced by apelin-13. Down-regulation of Notch3 using small interfering RNA inhibits the expression of Cyclin D1 and prevents apelin-13-induced VSMC proliferation. In conclusion, Jagged-1/Notch3 signaling transduction pathway is involved in VSMC proliferation induced by apelin-13.
关键词：
copper;alkynes;trifluoromethylation;S-(trifluoromethyl)diarylsulfonium salt
摘要：
The copper-mediated trifluoromethylation of terminal alkynes with S-(trifluoromethyl)diarylsulfonium salt has been carefully investigated. The reactions proceeded smoothly to afford trifluoromethylated acetylenes in moderate to good yields. This approach is a convenient method to synthesize a variety of functional trifluoromethylated acetylenes.
作者机构：
[Yu, Xiaohua; Zhao, Guojun; Yin, Kai; Li, Xiaoxu; Tang, Chaoke; Jiang, Zhisheng; Xiao, Ji; Mo, Zhongcheng] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Yu, Xiaohua] Univ S China, Sch Nursing, Hengyang 421001, Peoples R China.;[Fu, Yuchang] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.;[Zha, Xiaohui] Univ Ottawa, Ottawa Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada.
通讯机构：
[Tang, Chaoke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
Niemann–Pick type C1;oxLDL;ERK1/2;COX-2;PPARα;cholesterol
摘要：
The Niemann–Pick type C1 (NPC1) is located mainly in the membranes of the late endosome/lysosome and controls the intracellular cholesterol trafficking from the late endosome/lysosome to the plasma membrane. It has been reported that oxidized low-density lipoprotein (oxLDL) can up-regulate NPC1 expression. However, the detailed mechanisms are not fully understood. In this study, we investigated the effect of oxLDL stimulation on NPC1 expression in THP-1 macrophages. Our results showed that oxLDL up-regulated NPC1 expression at both mRNA and protein levels in a dose-dependent and time-dependent manner. In addition, oxLDL also induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Treatment with oxLDL significantly increased cyclooxygenase-2 (COX-2) mRNA and protein expression in the macrophages, and these increases were suppressed by the ERK1/2 inhibitor PD98059 or ERK1/2 small interfering RNA (siRNA) treatment. OxLDL up-regulated the expression of peroxisome proliferator-activated receptor α (PPARα) at the mRNA and protein levels, which could be abolished by COX-2 siRNA or COX-2 inhibitor NS398 treatment in these macrophages. OxLDL dramatically elevated cellular cholesterol efflux, which was abrogated by inhibiting ERK1/2 and/or COX-2. In addition, oxLDL-induced NPC1 expression and cellular cholesterol efflux were reversed by PPARα siRNA or GW6471, an antagonist of PPARα. Taken together, these results provide the evidence that oxLDL can up-regulate the expression of the NPC1 through ERK1/2/COX-2/PPARα-signaling pathway in macrophages.
