作者机构：
[Lu He; Lanfang Li; Jin Xu; Qun Zhou; Di Wu; Meiqing liu; Zhe Chen; Hong Zhou; Linxi Chen] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China
作者机构：
Institute of Cardiovascular Disease,University of South China, Key Laboratory for Arteriosclerology of Hunan Province;[Li Lanfang] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, 421001;Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, 421001;Institute of Cardiovascular Disease, University of South China, Key Laboratory for Arteriosclerology of Hunan Province, Hengyang, 421001;[Li Lanfang] Institute of Cardiovascular Disease,University of South China, Key Laboratory for Arteriosclerology of Hunan Province
通讯机构：
[Linxi Chen *] 2;[Zhisheng Jiang *] 1;2 Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study , Institute of Pharmacy and Pharmacology , Learning Key Laboratory for Pharmacoproteomics , University of South China , Hengyang 421001 , China<&wdkj&>1 Institute of Cardiovascular Disease , Key Laboratory for Arteriosclerology of Hunan Province , University of South China , Hengyang 421001 , China
关键词：
initially;identified;closest
摘要：
APJ, which was initially identified as a gene with closest homology to the angiotensin II type 1 receptor, is a seven transmembrane G protein-coupled receptor. Apelin is an endogenous ligand of the APJ originally isolated from bovine stomach extracts. There are several isoforms of apelin. Apelin preproproteins contain 77 amino-acid residues, which can be cleaved to form shorter bioactive isoforms, including apelin-36, apelin-17, apelin-13, apelin-12, and so on. Apelin/APJ receptor is extensively distributed in the central nervous system and peripheral tissues. Apelin/APJ system involves in a wide range of physiological and pathological functions. For example, apelin lowers blood pressure via a NO/cGMP-dependent mechanism. Apelin-13 maintains the Ca~(2+) transient against ischemia/reperfusion in cardiomyocytes. Furthermore, apelin-13 promotes cell proliferation and angiogenesis via PI3K/AKT activation.
作者机构：
[Li, Lanfang; Jiang, Zhisheng] Univ South China, Postdoctoral Mobile Stat Basic Med, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Li, Lanfang; He, Lu; Wu, Di; Chen, Linxi] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
通讯机构：
[Chen, Linxi] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
关键词：
Pannexin-1;ATP;arrhythmia;cardiac fibrosis
摘要：
Pannexin-1, Pannexin-2, and Pannexin-3 are three members of the Pannexin family of channel-forming glycoprotein. Their primary function is defined by their ability to form single-membrane channels. Pannexin-1 ubiquitously exists in many cells and organs throughout the body and is specially distributed in the circulatory system, while the expressions of Pannexin-2 and Pannexin-3 are mostly restricted to organs and tissues. Pannexin-1 oligomers have been shown to be functional single membrane channels that connect intracellular and extracellular compartments and are not intercellular channels in appositional membranes. The physiological functions of Pannexin-1 are to link to the adenosine triphosphate efflux that acts as a paracrine signal, and regulate cellular inflammasomes in a variety of cell types under physiological and pathophysiological conditions. However, there are still many functions to be explored. This review summarizes recent reports and discusses the role of Pannexin-1 in cardiovascular diseases, including ischemia, arrhythmia, cardiac fibrosis, and hypertension. Pannexin-1 has been suggested as an exciting, clinically relevant target in cardiovascular diseases.
摘要：
Apelin is highly expressed in rat left ventricular hypertrophy Sprague Dawley rat models, and it plays a crucial role in the cardiovascular system. The aim this study was to clarify whether apelin-13 promotes hypertrophy in H9c2 rat cardiomyocytes and to investigate its underlying mechanism. The cardiomyocyte hypertrophy was observed by measuring the diameter, volume, and protein content of H9c2 cells. The activation of autophagy was evaluated by observing the morphology of autophagosomes by transmission electron microscopy, observing the subcellular localization of LC3 by light microscopy, and detecting the membrane-associated form of LC3 by western blot analysis. The phosphatidylinositol 3-kinase (PI3K) signaling pathway was identified and the proteins expression was detected using western blot analysis. The results revealed that apelin-13 increased the diameter, volume, and protein content of H9c2 cells and promoted the phosphorylation of PI3K, Akt, ERK1/2, and p70S6K. Apelin-13 activated the PI3K-Akt-ERK1/2-p70S6K pathway. PI3K inhibitor LY294002, Akt inhibitor 1701-1, ERK1/2 inhibitor PD98059 attenuated the increase of the cell diameter, volume, protein content induced by apelin-13. Apelin-13 increased the autophagosomes and up-regulated the expressions of beclin 1 and LC3-II/I both transiently and stably. The autophagy inhibitor 3MA ameliorated the increase of cell diameter, volume, and protein content that were induced by apelin-13. These results suggested that apelin-13 promotes H9c2 rat cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy.
作者机构：
[Feng XIE; Di WU; Jiangang CAO; Hening LI; Lu HE; Meiqing LIU; Lanfang LI; Linxi CHEN] Institute of Pharmacy and Pharmacology,Learning Key Laboratory for Pharmacoproteomics,University of South China;[Feng XIE; Di WU; Jiangang CAO; Hening LI; Lu HE; Meiqing LIU; Lanfang LI; Linxi CHEN] Nanshan District Maternity & Child Healthcare Hospital of Shenzhen
摘要：
Aims: Apelin is the endogenous ligand for the G protein coupled receptor APJ.It promotes vascular smooth muscle cell proliferation and monocyte adhesion to endothelial cells.In our previous research,we found that apelin-13 promotes H9c2 rat cardiomyocytes hypertrophy by PI3K-Akt-ERK1/2-p70S6K and PI3K-autophagy pathway.The objective of this study was to explore the role of apelin-13 on the regulation of ER stress and autophagy,And then to investigate the association of ER stress and autophagy with the improvement of cell diameter,cell volume after giving apelin-13.Methods and results: Fuorescence microscope analysis exhibited that apelin-13 increases the production of ROS in a dose dependent manner.Electron microscope observation reflected that apelin-13(1μmol/L) activate the endoplasmic reticulum stress.Western Blot results show that apelin-13 promotes the expression of NOX4,Bip and CHOP in dose and time dependent manners.APJ shRNA,NOX4 inhibitor dibenziodolium chloride (DPI) block the increase of Bip,CHOP induced by apelin-13(1μmol/L).Apelin-13 promotes the expression of LC3-Ⅱ/Ⅰ,beclin 1and reduce the expression of p62 in dose and time dependent manners.APJ shRNA,NOX4 inhibitor DPI,endoplasmic reticulum stress inhibitor Salubrinal(10μmol/L),Bip siRNA and CHOP siRNA all can attenuate the overexpression of LC3-Ⅱ/Ⅰ,beclin 1 and cripple the decrease of p62 induced by apelin-13(1μmol/L);Scepter TM Handheld Automated Cell Counter data explain that endoplasmic reticulum stress inhibitor Salubrinal(10μmol/L),Bip siRNA,CHOP siRNA or autophagy inhibitor 3MA(5mmol/L)all weaken the increase of cell diameter,volume and intracellular protein content induced by apelin-13(2μmol/L);Endoplasmic reticulum stress revulsant Tunicamycin(1mg/L) enhanced the increase of cell diameter,volume and intracellular protein content induced by apelin-13(2μmol/L).Conclusion: These findings show that ER stress-autophagy involved in the H9c2 rat cardiomyocytes hypertrophy induced by apelin-13.
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.
作者机构：
[Rongbin Huang; Xiang Lei; Xuan Cao; Lanfang Li; Guotao Tang] Institute of Pharmacy and Pharmacology,University of South China,Hengyang,Hunan,421001,People's Republic of China
摘要：
<正>pH-sensitive amphiphilic poly(ethylene glycol)-imine-benzoic-dipalmitate(PEG-I-dC16)polymers with two different PEGs molecular weight were designed and synthesized.The molecular structures of the p
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
