摘要：
Since Ashford and Porter first discovered that cells ＂eat themselves＂ in 1962, the process known as autophagy has generated intense interest in both biomedical research and clinical medicine. Autophagy is a regulated cellular pathway that transports damaged, modified or aging organelles and proteins to lysosomes/vacuoles for degradation.
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.
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.
作者机构：
[陈临溪; 李兰芳; 杨莉; 柳威; 秦旭平; 高晶] Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, Hunan Province, China;Hunan Polytechnic College of Environment and Biology, Hengyang 421005, Hunan Province, China;[毛小环] Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, Hunan Province, China, Hunan Polytechnic College of Environment and Biology, Hengyang 421005, Hunan Province, China
通讯机构：
[Chen, L.-x.] I;Institute of Pharmacy and Pharmacology, , Hengyang 421001, Hunan Province, China
摘要：
Previously, we found that G protein-coupled receptor APJ endogenous ligand apelin-13 stimulates vascular smooth muscle cells (VSMC) proliferation mediated in part by PKC-PI3K-ERK1/2-cyclinDl signaling cascades. In this study, Raf-1-14-3-3 signaling in rat VSMCs proliferation stimulated by apelin-13 was further investigated. Cell proliferation was measured with MTT assay. Expression of PI3K, phospho-PI3K, Raf-1, phospho-Raf-1, ERK1/2, phospho-ERKl/2, cyclinDl and cyclinE were detected by Western blotting. 14-3-3 protein combining with Raf-1 was detected by immunoprecipitation. Here, we demonstrated that apelin-13 increased the expression of 14-3-3, Raf-1 phosphorylation and ERK1/2 phosphorylation in a concentration- dependent and time-dependent manner at 0~4 μmol/L and 0~48 h. 14-3-3 inhibitor Difopein decreased the apelin-13-induced Raf-1 phosphorylation, ERK1/2 phosphorylation, expression of cyclinDl and cyclinE. Furthermore, apelin-13 promoted the combination of 14-3-3 protein and Raf-1, Difopein significantly inhibited the combination of 14-3-3 and Raf-1 stimulated by apelin-13. Similarly, Difopein significantly inhibited the VSMCs proliferation stimulated by apelin-13. Our results revealed that Raf-1 +14-3-3-ERK1/2 signaling cascades mediated the effect of apelin-13 on rat VSMCs proliferation.
摘要：
Previously we reported that G protein-coupled receptor APJ endogenous ligand apelin-13 induced adhesion of monocytes to human umbilical vein endothelial cells (HUVECs).Now we investigated whether phosphatidylinositol 3-kinase (PI3K) signaling pathway mediated monocytes (MCs) adhesion to HUVECs induced by apelin-13. Human umbilical vein endothelial cell line ECV304 was cultured in DMEM medium and the monocyte cell line THP-1 was cultured in 1640 medium. Myeloperoxidase(MPO) assay was used to identify effects of monocytes adhesion to HUVECs. Expression of vascular cell adhesion molecule (VCAM)-1, phospho-PI3K and PI3K were detected by Western blotting. Apelin-13 promoted PI3K phosphorylation in concentration-dependent and time-dependent manner, which reached the peak at 1 mu mol/L and 30 min respectively. The PI3K inhibitor LY294002 inhibited PI3K phosphorylation and the expression of VCAM-1 in HUVECs induced by apelin-13. And the PI3K inhibitor LY294002 inhibited the MCs adhesion to HUVECs induced by apclin-13. It can be concluded that apelin-13 promoted monocytes adhesion to HUVECs through VCAM-1 mediated by PI3K signaling pathway.
摘要：
To investigate whether apelin-13 induced THP-1 monocytes (MCs) adhesion to ECV304 human umbilical vein endothelial cells (HUVECs) via 14-3-3 signaling transduction pathway and the potential novel physiological function and signaling transduction pathway of apelin-APJ, HUVECs ECV304 were cultured in DMEM and MCs THP-1 were cultured in RPMI 1640 medium. Monocyte adhesion and the expression of vascular cell adhesion molecule-1 (VCAM-1) and 14-3-3 were measured with monocyte adhesion assay and western blot analysis. Data showed that apelin-13 increased adhesion of MCs to HUVECs in a concentration- and time-dependent manner, which reached their peaks at 1 µM and 12 h, respectively. Similarly, apelin-13 induced the expression of HUVECs adhesion molecule, VCAM-1, in a concentration- and time-dependent manner, reached their peaks at 1 µM and 12 h, respectively. Apelin-13 induced the expression of 14-3-3 in a concentration- and time-dependent manner, which reached their peaks at 1 µM and 5 min, respectively. Furthermore, the potent 14-3-3 inhibitor difopein significantly reduced the expression of 14-3-3 and VCAM-1 in apelin-13 stimulated HUVECs, and difopein significantly inhibited the effect of apelin-13 on induction of MCs adhesion to HUVECs. These data suggested that 14-3-3 mediated the induction of adhesion of MCs to HUVECs by Apelin-13.
摘要：
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 and nervous systems. Importantly, APJ is also involved in the pathogenesis if HIV-1 infection. We investigated whether vascular smooth muscle cell proliferation was regulated through an apelin-pERK1/2-cyclin D1 signal transduction pathway. Apelin-13 significantly stimulated vascular smooth muscle cell proliferation and increased cell cycle progression. Apelin-13 a decreased the proportion of cell in the G0/G1 phase while increasing the number of cells in S phase. Apelin-13 also increased the levels of cyclin D1, cyclin E and pERK1/2. Treatment of cells with the MEK inhibitor PD98059 attenuated the apelin-3-induced pERK1/2 activation. Similarly, treatment with PD98059 partially diminished the apelin-13-induced expression of cyclin D1 and vascular smooth muscle cell proliferation. Taken together, these data established that apelin-13 stimulates vascular smooth muscle cell proliferation by promoting the G1-S phase transition, and that this effect is mediated in part by an apelin-pERKl/2-cyclin D1 signal cascade.
通讯机构：
[Pan, W.-N.] I;Institute of Pharmacy and Pharmacology, University of South China, China
关键词：
血管平滑肌细胞;细胞周期蛋白
摘要：
目的研究G蛋白偶联受体APJ（血管紧张素受体样受体或称血管紧张素受体AT．相关的受体蛋白，putative receptor protein related to the angiotensinreceptor AT_1）的内源性配体apelin-13通过PKC—ERK1／2-Cyclins信号通路促进大鼠血管平滑肌细胞（vascular smooth muscle cells，VSMCs）增殖的影响。方法培养SD大鼠胸主动脉VSMCs，Western blot检测p-ERK1／2、ERK1／2、细胞周期蛋白CyclinDl和CyclinE的表达，四噻唑蓝比色法观察PKC阻断剂GF109203X对apelin-13促大鼠VSMCs增殖的影响。结果Apelin-13剂量依赖性和时间依赖性地促进大鼠VSMCsp-ERK1／2表达增加，对ERK1／2表达没有明显影响，GF109203X可明显抑制apelin-13诱导的细胞增殖及p-ERK1／2、CyclinDl和CyclinE的表达。结论Apelin-13促进大鼠VSMCs增殖可能与apelin—APJ—PKC—ERK1／2-Cyclins信号通路有关。
