作者机构：
[刘彦梅; 骆镜妃; 郭锋; 全海燕; 彭虹艳] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China;[秦旭平] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China. qinxuping@sohu.com
摘要：
The aim of this study was to investigate the role of apelin in the cell proliferation and autophagy of lung adenocarcinoma. The over-expression of APJ in lung adenocarcinoma was detected by immunohistochemistry, while plasma apelin level in lung cancer patients was measured by enzyme-linked immunosorbent assay. Our findings revealed that apelin-13 significantly increased the phosphorylation of ERK1/2, the expression of cyclin D1, microtubule-associated protein 1 light chain 3A/B (LC3A/B), and beclin1, and confirmed that apelin-13 promoted A549 cell proliferation and induced A549 cell autophagy via ERK1/2 signaling. Moreover, there are pores on the surface of human lung adenocarcinoma cell line A549 and apelin-13 causes cell surface smooth and glossy as observed under atomic force microscopy. These results suggested that ERK1/2 signaling pathway mediates apelin-13-induced lung adenocarcinoma cell proliferation and autophagy. Under our experimental condition, autophagy associated with 3-methyladenine was not involved in cell proliferation.
作者机构：
[Jiangang Cao; Deguan Lv; Li Yin; Feng Xie; Yao Li; Hening Li; Xuping Qin; Lanfang Li; Linxi Chen] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmaco-proteomics,University of South China, Hengyang, Hunan 421001, China
摘要：
This study is designed to investigate whether APJ receptor acts as a sensor in static pressure-induced cardiomyocyte hypertrophy and to investigate the mechanism of PI3K-autophagy pathway. The left ventricular hypertrophy rat model was established by coarctation of abdominal aorta. H9c2 rat cardiomyocytes were cultured in the presence of static pressure which was given by a custom-made pressure incubator. The results revealed that the expression of apelin/APJ system, PI3K, Akt and their phosphorylation were significantly increased in the operation group. Static pressure up-regulated the APJ expression, PI3K phosphorylation, Akt phosphorylation, LC3-II/I and beclin-1 expression in cardiomyocytes. APJ shRNA pGPU6/Neo-rat-399, PI3K inhibitor LY294002, Akt inhibitor 1701-1 blocked the up-regulation of APJ, PI3K phosphorylation, Akt phosphorylation, LC3-II/I and beclin-1 expression, respectively. Moreover, static pressure increased the diameter, volume, protein content of cells, and these could be reversed when the cells were treated with pGPU6/Neo-rat-399, LY294002, and autophagy inhibitor 3-methyladenine, respectively. These results suggested that static pressure up-regulates APJ expression to promote cardiomyocyte hypertrophy by a PI3K-autophagy pathway.
摘要：
Aim To determine the role of receptor component protein (RCP) in calcitonin gene-related peptide (CGRP) and angiotensin Ⅱ signal transduction in action of vascular peroxidase-1 (VPO1) in VSMC.Methods Mouse vascular smooth muscle cell line A10 (A10VSMC) was employed in the study.Western blot was used to detect the expression of RCP and VPO1 protein.RT-PCR was used to detect the expression of RCP and VPO1 mRNA.RCP-specific small interference RNA (RCP-siRNA) was used to silence oligonucleotide sequence co-immunoprecipitation was used to determine interaction of RCP and Gαs/Gβ/Gγ Results Both CGRP and angiotensin Ⅱ up-regulated the expression of RCP while CGRP down-regulated the expression of RCP induced by angiotensin Ⅱ in VSMC;Angiotensin Ⅱ up-regulated the expression of VPO1 in a concentration and time-dependent manner in VSMC;CGRP inhibited the expression of VPO1 induced by angiotensin Ⅱ and the effect of CGRP was enhanced by Catalase, H2O2 scavenger.RCP-siRNA successfully decreased RCP protein expression by ~80% in 48 h, following with an decrease in VPO1 expression in CGRP and/or angiotensin Ⅱ induced VSMC In addition, RCP co-immunoprecipitated with Gαs and Gβ but not with Gγ in VSMC.Conclusion RCP may contribute to the inhibitory effect of CGRP on angiotensin Ⅱ induced VPO1 expression in VSMC, and the mechanism may be related to the interactions between RCP and Gαs / Gβ.
作者：
YAN GLi;SU Tao;LV De-Guan;XIE Feng;LIU Wei;...
作者机构：
[YAN GLi; SU Tao; LV De-Guan; XIE Feng; LIU Wei; CAO Jian-Gang; QIN Xu-Ping; LI Lan-Fang; CHEN Lin-Xi] Institution of Pharmacy and Pharmacology,University of South China,Learning Key Laboratory for Pharmaco-proteomics;[YAN GLi; SU Tao; LV De-Guan; XIE Feng; LIU Wei; CAO Jian-Gang; QIN Xu-Ping; LI Lan-Fang; CHEN Lin-Xi] Pharmaceutical Department,Jingzhou First People’s Hospital;[YAN GLi; SU Tao; LV De-Guan; XIE Feng; LIU Wei; CAO Jian-Gang; QIN Xu-Ping; LI Lan-Fang; CHEN Lin-Xi] First Affiliated Hospital of Yangtze University
会议名称：
2013医学前沿论坛暨第十三届全国肿瘤药理与化疗学术会议
会议时间：
2013-5-5
会议地点：
洛阳
会议主办单位：
中国药理学会;中国抗癌协会;中国工程院医药卫生学部
会议论文集名称：
2013医学前沿论坛暨第十三届全国肿瘤药理与化疗学术会议论文集
关键词：
Apelin;A549;ERK1/2;proliferation;autophagy
摘要：
<正>The aim of the study was to investigate the role that apelin has played in the proliferation and autophagy of lung adenocarcinoma.Bioinformatics analysis revealed the distribution of APJ in various tissues and whether or not APJ exist in lung adenocarcinoma cell line A549.0verexpression of APJ in lung adenocarcinoma was detected by immunohistochemistry
作者机构：
[Lv Deguan; Lu Qixuan; Li Yao; Cao Jianguang; Yang Lingfang; Liu Meiqing; Zhang Hanjing; Qin Xuping; Li Lanfang; Chen Linxi] Institute of pharmacy and pharmacology,University of South China,Hengyang,Hunan,421001
摘要：
<正>Background and objective:Apelin is a newly discovered bioactive peptides which had been proved to be an endogenous ligand of the APJ receptor.Recent evidences had confirmed that apelin is a novel c
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：
To determine whether caveolae and caveolin-1 affect the distribution of calcitonin receptor-like receptors (CLR) in vascular smooth muscle cell (VSMC) membranes, we have used VSMCs cell line A10. We found that calcitonin gene-related peptide (CGRP) reduced CLR protein in the VSMC membrane in a time-dependent manner, which was dramatically decreased after 4 h CGRP treatment, and remained at a low level after 16 h. CGRP8-37 or β-cyclodextrin (β-CD) blocked this effect, without changing the total levels of CLR protein and mRNA in the cells. Co-immunoprecipitation experiments showed that CLR bound to caveolin-1 in cell membrane fractions. Confocal laser microscopic studies confirmed this co-localization relationship at the cell plasma membrane. Thus, our data indicate that the structural integrity of caveolae plays an important role in regulating subcellular distribution of CLR.
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：
[陈根; 林杰; 秦旭平] Institute of Drug and Pharmacology, University of South China, Hengyang 421001, China;[李洁] The First People's Hospital of Chenzhou, Chenzhou 423000, China;[王俊杰] Xiang Nan University, Chenzhou 423000, China;[周楠] Medical College, Xi 'an Jiaotong University, Xi 'an 710061, China
通讯机构：
Institute of Drug and Pharmacology, University of South China, China
作者机构：
[XIE Feng; LIU Wei; FENG Feng; LI Xin; YANG Li; LU Qi-xuan; QIN Xu-ping; LI Lan-fang; CHEN Lin-Xi] Institude of Pharmacy and Pharmacology,University of South China,Learning Key Laboratory for Pharmaco-proteomics
摘要：
<正>AIM:APJ is an orphan G protein - coupled receptor and its endogenous ligand is apelin.The objective of this work is to study whether apelin can promote rat myocardial hypertrophy and autophagy regu
作者机构：
[李兰芳; 李峰; 杨莉; 毛小环; 柳威; 谢凤; 秦旭平; 郭玉; 陈临溪] Institute of Pharmacy and Pharmacology,University of South China;[李兰芳; 李峰; 杨莉; 毛小环; 柳威; 谢凤; 秦旭平; 郭玉; 陈临溪] Department of Physiology,Hunan College of Traditional Chinese Medicine;[李兰芳; 李峰; 杨莉; 毛小环; 柳威; 谢凤; 秦旭平; 郭玉; 陈临溪] Institute of Pharmacy and Pharmacology,University of South China,
会议名称：
中国活性氧生物学效应学术会议
会议时间：
2011-09-01
会议地点：
中国陕西西安
会议论文集名称：
中国活性氧生物学效应学术会议论文集（第一册）
摘要：
<正>Apelin is the endogenous ligand of the G protein coupled receptor,APJ.Vascular smooth muscle cells express both apelin and APJ,which are important regulatory factors in the cardiovascular systems. Previourly we reported that apelin-13 significantly stimulated vascular smooth muscle cell proliferation. However,little is known about the precise cellular mechanisms responsible for vascular smooth muscle cell proliferation induced by apelin-13.Here,we present novel data that indicate the key role of NADPH oxidase-derived reactive oxygen species in vascular smooth muscle cell proliferation treated by apelin-13. Apelin-13 stimulated reactive oxygen species production in a concentration and time-dependent manner. And DPI,a NADPH oxidase inhibitor,impaired apelin-13-induced reactive oxygen species generation and vascular smooth muscle cells proliferation.Apelin-13-treatment increased the expression of NADPH oxidase 4 in a dose-dependent manner.Down-regulation of NADPH oxidase 4 using siRNA prevented apelin-13-induced reactive oxygen species generation and vascular smooth muscle cells proliferation.An increase in reactive molecules can trigger the activation of ERKl/2 stress-sensitive signaling pathways but not P38 and JNK.In conclusion,Apelin-13 induced the vascular smooth muscle cells proliferation by NOX4-derived ROS via ERK1/2 signal pathway.
