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.
作者机构：
[Wei, Hai-jun; Li, Man-hong; Tang, Ji-ping; Tang, Xiao-qing] Univ South China, Coll Med, Inst Neurosci, Hengyang 421001, Peoples R China.;[Xu, Jin-hua] Univ South China, Lab Ctr Biochem & Mol Biol, Hengyang 421001, Peoples R China.;[Li, Man-hong; Tang, Ji-ping; Zou, Wei; Zhang, Ping] Univ South China, Nanhua Affiliated Hosp, Dept Neurol, Hengyang 421001, Peoples R China.;[Wang, Li] Univ South China, Coll Med, Dept Anthropot, Hengyang 421001, Peoples R China.;[Wang, Chun-yan] Univ South China, Coll Med, Dept Pathophysiol, Hengyang 421001, Peoples R China.
通讯机构：
[Zhang, P ] Univ South China, Nanhua Affiliated Hosp, Dept Neurol, Hengyang 421001, Peoples R China.;Univ South China, Nanhua Affiliated Hosp, Dept Neurol, Hengyang 421001, Peoples R China.
关键词：
hydrogen sulfide;homocysteine;neurotoxicity;hippocampus;apoptosis;ER stress;BDNF;tyrosine protein kinase B;Alzheimer’s disease
摘要：
Aim: Homocysteine (Hcy) can elicit neuronal cell death, and hyperhomocysteinemia is a strong independent risk factor for Alzheimer's disease. The aim of this study was to examine the effects of hydrogen sulfide (H2S) on Hcy-induced endoplasmic reticulum (ER) stress and neuronal apoptosis in rat hippocampus. Methods: Adult male SD rats were intracerebroventricularly (icv) injected with Hcy (0.6 μmol/d) for 7 d. Before Hcy injection, the rats were treated with NaHS (30 or 100 μmol·kg−1·d−1, ip) and/or k252a (1 μg/d, icv) for 2 d. The apoptotic neurons were detected in hippocampal coronal slices with TUNEL staining. The expression of glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), cleaved caspase-12, and BDNF in the hippocampus were examined using Western blotting assays. The generation of H2S in the hippocampus was measured with the NNDPD method. Results: Hcy markedly inhibited the production of endogenous H2S and increased apoptotic neurons in the hippocampus. Furthermore, Hcy induced ER stress responses in the hippocampus, as indicated by the upregulation of GRP78, CHOP, and cleaved caspase-12. Treatment with the H2S donor NaHS increased the endogenous H2S production and BDNF expression in a dose-dependent manner, and significantly reduced Hcy-induced neuronal apoptosis and ER stress responses in the hippocampus. Treatment with k252a, a specific inhibitor of TrkB (the receptor of BDNF), abolished the protective effects of NaHS against Hcy-induced ER stress in the hippocampus. Conclusion: H2S attenuates ER stress and neuronal apoptosis in the hippocampus of Hcy-treated rats via upregulating the BDNF-TrkB pathway.
期刊：
Acta Biochimica et Biophysica Sinica,2013年45(10):875-881 ISSN：1672-9145
通讯作者：
Chen, Linxi
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] 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.
摘要：
Aim: To investigate the potential antidepressant and anxiolytic effects of Neu-P11, a novel melatonin agonist, in two models of depression in rats and a model of anxiety in mice. Methods: In the learned helplessness test (LH), Neu-P11 or melatonin (25-100 mg/kg, ip) was administered to rats 2 h before the beginning of the dark phase once a day for 5 days and the number of escape failures and intertrial crossings during the test phase were recorded. In the forced swimming test (FST), rats received a single or repeated administration of Neu-P11 (25-100 mg/kg, ip). The total period of immobility during the test phase was assessed. In the elevated plus-maze test (EPM), mice were treated with Neu-P11 (25-100 mg/kg, ip) or melatonin in the morning or in the evening and tested 2 h later. The percentage of time spent in the open arms and the open arms entries were assessed. Results: In the LH test, Neu-P11 but not melatonin significantly decreased the escape deficit and had no effect on the intertrial crossings. In the FST, a single or repeated administration of Neu-P11, either in the morning or in the evening, significantly decreased the duration of immobility. In the EPM test, Neu-P11 significantly increased the percentage of time spent in the open arms and the open arms entries irrespective to the time of administration. Melatonin was effective only when administered in the afternoon. Conclusion: The results demonstrate that Neu-P11 exerts antidepressant and anxiolytic activities in rodent models.
摘要：
Hypoxia is a key component of the tumor microenvironment and represents a well-documented source of therapeutic failure in clinical oncology. Recent work has provided support for the idea that non-coding RNAs, and in particular, microRNAs, may play important roles in the adaptive response to low oxygen in tumors. Specifically, all published studies agree that the induction of microRNA-210 (miR-210) is a consistent feature of the hypoxic response in both normal and malignant cells. miR-210 is a robust target of hypoxia-inducible factors, and its overexpression has been detected in a variety of diseases with a hypoxic component, including most solid tumors. High levels of miR-210 have been linked to an in vivo hypoxic signature and to adverse prognosis in breast and pancreatic cancer patients. A wide variety of miR-210 targets have been identified, pointing to roles in mitochondrial metabolism, angiogenesis, DNA damage response, apoptosis, and cell survival. Such targets are suspected to affect the development of tumors in multiple ways; therefore, an increased knowledge about miR-210's functions may lead to novel diagnostic and therapeutic approaches in cancer.
作者机构：
[Tang, Chao-ke; Liao, Duan-fang; Sun, Shao-wei] Univ S China, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Chen, Lin-xi; Liao, Duan-fang; Lei, Xiao-yong; Tuo, Qin-hui; Sun, Shao-wei; Zu, Xu-yu] Univ S China, Inst Pharm & Pharmacol, Prov Key Lab Pharmacoprotom, Hengyang 421001, Peoples R China.;[Liao, Duan-fang] Hunan Univ Chinese Med, Dept Tradit Chinese Diagnost, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Li, Kai] Suzhou Univ, Mol Med Ctr, Suzhou 215004, Peoples R China.;[Li, Kai] Suzhou Univ, Affiliated Hosp 2, Suzhou 215004, Peoples R China.
通讯机构：
[Tang, Chao-ke] Univ S China, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.
关键词：
caveolae;caveolin-1;oxidized low density lipoprotein;atherosclerosis;transcytosis;human umbilical vein endothelial cells
摘要：
Aim: To explore the mechanisms involved in ox-LDL transcytosis across endothelial cells and the role of caveolae in this process. Methods: An in vitro model was established to investigate the passage of oxidized low density lipoprotein (ox-LDL) through a tight monolayer of human umbilical vein endothelial cells (HUVEC) cultured on a collagen-coated filter. Passage of Dil-labeled ox-LDL through the monolayer was measured using a fluorescence spectrophotometer. The uptake and efflux of ox-LDL by HUVEC were determined using fluorescence microscopy and HPLC. Results: Caveolae inhibitors - carrageenan (250 μg/mL), filipin (5 μg/mL), and nocodazole (33 μmol/L)-decreased the transport of ox-LDL across the monolayer by 48.9%, 72.4%, and 79.8% as compared to the control group. In addition, they effectively decreased ox-LDL uptake and inhibited the efflux of ox-LDL. Caveolin-1 and LOX-1 were up-regulated by ox-LDL in a time-dependent manner and decreased gradually after depletion of ox-LDL (P<0.05). After treatment HUVEC with ox-LDL and silencing caveolin-1, NF-KB translocation to the nucleus was blocked and LOX-1 expression decreased (P<0.05). Conclusion: Caveolae can be a carrier for ox-LDL and may be involved in the uptake and transcytosis of ox-LDL by HUVEC
摘要：
Objective This review discusses the current status and progress in studies on the roles of hydrogen sulfide (H(2)S) in regulation of neurotoxicity, neuroprotection, and neuromodulator, as well as its therapeutic potential for neurodegenerative disorders. Data sources The data used in this review were mainly from Med line and Pub Med published in English from 2001 to August 2011. The search terms were "hydrogen sulfide", "neuron", and "neurodegenerative disorders". Study selection Articles regarding the regulation of neuronal function, the protection against neuronal damage and neurological diseases, and their possible cellular and molecular mechanisms associated with H(2)S were selected. Results The inhibited generation of endogenous H(2)S is implicated in 1-methy-4-phenylpyridinium ion, 6-OHDA, and homocysteine-triggered neurotoxicity. H(2)S elicits neuroprotection in Alzheimer's disease and Parkinson's disease models as well as protecting neurons against oxidative stress, ischemia, and hypoxia-induced neuronal death. H(2)S offers anti-oxidant, anti-inflammatory and anti-apoptotic effects, as well as activates ATP-sensitive potassium channels and cystic fibrosis transmembrane conductance regulator Cl(-) channels. H(2)S regulates the long-term potentiation (LTP) and GABA(B) receptors in the hippocampus, as well as intracellular calcium and pH homeostasis in neurons and glia cells. Conclusions These articles suggest that endogenous H(2)S may regulate the toxicity of neurotoxin. H(2)S not only acts as a neuroprotectant but also serves as a novel neuromodulator. Chin Med J 2011;124(21):3576-3582
作者机构：
[Zhao, Guo-jun; Tang, Chao-ke; Liu, Mei-mei; Tan, Chun-zhi; Liu, Xie-hong; Yin, Wei-dong; Yin, Kai; Jiang, Jin; Mo, Zhong-cheng; Cui, Li-bao; Xiao, Ji; Chen, Si-guo] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Xiao, Ji] Univ S China, Dept Anesthesiol, Affiliated Hosp 2, Hengyang 421001, Peoples R China.;[Chen, Si-guo] Xiangnan Univ, Dept Physiol, Chenzhou 423000, Peoples R China.
通讯机构：
[Tang, Chao-ke] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
ATP-binding membrane cassette transporter A-l;ATP-binding membrane cassette transporter G-l;ibrolipim;liver X receptor α;atherosclerosis;RNA interference;high density lipoprotein;apolipoprotein;cholesterol;ATP-binding membrane cassette transporter A-l;ATP-binding membrane cassette transporter G-l;ibrolipim;liver X receptor α;atherosclerosis;RNA interference;high density lipoprotein;apolipoprotein;cholesterol
摘要：
To determine the effects and potential mechanisms of ibrolipim on ATP-binding membrane cassette transporter A-1 (ABCA1) and ATP-binding membrane cassette transporter G-1 (ABCG1) expression from human macrophage foam cells, which may play a critical role in atherogenesis. Human THP-1 cells pre-incubated with ox-LDL served as foam cell models. Specific mRNA was quantified using real-time RT-PCR and protein expression using Western blotting. Cellular cholesterol handling was studied using cholesterol efflux experiments and high performance liquid chromatography assays. Ibrolipim 5 and 50 μmol/L significantly increased cholesterol efflux from THP-1 macrophage-derived foam cells to apoA-I or HDL. Moreover, it upregulated the expression of ABCA1 and ABCG1. In addition, LXRα was also upregulated by the ibrolipim treatment. In addition, LXRα small interfering RNA completely abolished the promotion effect that was induced by ibrolipim. Ibrolipim increased ABCA1 and ABCG1 expression and promoted cholesterol efflux, which was mediated by the LXRα signaling pathway.
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.
摘要：
AIM: To investigate the effect of 5-allyl-7-gen-difluoromethylenechrysin (ADFMChR) on apoptosis of human liver carcinoma HepG2 cell line and the molecular mechanisms involved. METHODS: HepG2 cells and L-02 cells were cultured in vitro and the inhibitory effect of ADFMChR on their proliferation was measured by MTT assay. The apoptosis of HepG2 cells was determined by flow cytometry (FCM) using propidium iodide (PI) fluorescence staining. DNA ladder bands were observed by DNA agarose gel electrophoresis. The influence of ADFMChR on the proxisome proliferator-activated receptor gamma (PPAR gamma), NF-kappa B, Bcl-2 and Bax protein expression of HepG2 cells were analyzed by Western blotting. RESULTS: MTT assay showed that ADFMChR significantly inhibited proliferation of HepG2 cells in a dose-dependent manner, with little effect on growth of L-02 cells, and when IC50 was measured as 8.45 mu mol/L and 191.55 mu mol/L respectively, the potency of ADFMChR to HepG2 cells, was found to be similar to 5-fluorouracil (5-FU, IC50 was 9.27 mu mol/L). The selective index of ADFMChR cytotoxicity to HepG2 cells was 22.67 (191.55/8.45), higher than 5-FU (SI was 7.05 (65.37/9.27). FCM with PI staining demonstrated that the apoptosis rates of HepG2 cells treated with 3.0, 10.0 and 30.0 mu mol/L ADFMChR for 48 h were 5.79%, 9.29% and 37.8%, respectively, and were significantly higher when treated with 30.0 mu mol/L ADFMChR than when treated with 30.0 mu mol/L ChR (16.0%) (P < 0.05) and were similar to those obtained with 30.0 mu mol/L 5-FU (41.0%). DNA agarose gel electrophoresis showed that treatment of HepG2 cells with 10.0 mu mol/L ADFMChR for 48 h and 72 h resulted in typical DNA ladders which could be reversed by 10.00 mu mol/L GW9662, a blocker of PPAR gamma. Western blotting analysis revealed that after 24 h of treatment with 3.0, 10.0, 30.0 mu mol/L ADFMChR, PPAR gamma and Bax protein expression in HepG2 cells increased but Bcl-2 and NF-kappa B expression decreased; however, pre-incubation with 10.0 mu mol/L GW9662 could efficiently antagonize and weaken the regulatory effect of 3.0, 30.0 mu mol/L ADFMChR on PPAR gamma and NF-kappa B protein expression in HepG2 cells. CONCLUSION: ADFMChR induces apoptosis of HepG2 cell lines by activating PPAR gamma, inhibiting protein expression of Bcl-2 and NF-kappa B, and increasing Bax expression. (C) 2009 The WJG Press and Baishideng. All rights reserved.
期刊：
Science China Life Sciences,2013年56(5):460-466 ISSN：1674-7305
通讯作者：
Li ZhongYu
作者机构：
[Wu YiMou; Cao WenJuan; Zhou Zhou; Lu ChunXue; Zhou Hui; Li ZhongYu; Ma KangKang] Univ South China, Pathogen Biol Inst, Hengyang 421001, Peoples R China.;[Xie XiaoBing; Zhou Hui] Hunan Univ Chinese Med, Hosp 1, Dept Lab Med, Changsha 410007, Hunan, Peoples R China.;[Huang QiuLin] Univ South China, Affiliated Hosp 1, Dept Gen Surg, Hengyang 421001, Peoples R China.;[Zhong GuangMing] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA.
通讯机构：
[Li ZhongYu] Univ South China, Pathogen Biol Inst, Hengyang 421001, Peoples R China.
关键词：
TLR2
摘要：
Infection with Chlamydia trachomatis induces inflammatory pathologies in the urogenital tract that can lead to infertility and ectopic pregnancy.Pathogenesis of infection has been mostly attributed to excessive cytokine production.However,precise mechanisms on how C.trachomatis triggers this production,and which protein(s) stimulate inflammatory cytokines remains unknown.In the present study,the C.trachomatis pORF5 protein induced tumor necrosis factor alpha(TNF-α),interleukin-1 beta(IL-1β) and interleukin-8(IL-8) in dose-and time-dependent manners in the THP-1 human monocyte cell line.We found that intracellular p38/mitogen-activated protein kinase(MAPK) and extracellular signal-regulated kinase(ERK)/MAPK signaling pathways were required for the induction of TNF-α,IL-1β and IL-8.Blockade of toll-like receptor 2(TLR2) signaling reduced induction levels of TNF-α,IL-8 and IL-1β.We concluded that the C.trachomatis pORF5 protein might contribute to the inflammatory processes associated with chlamydial infections.
期刊：
Acta Biochimica et Biophysica Sinica,2016年48(6):491-500 ISSN：1672-9145
通讯作者：
Chen, L.
作者机构：
[Li, Lanfang; Peng, Lijun; Zhong, Qiaoqing; Jiang, Zhisheng] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Postdoctoral Mobile Stat Basic Med, Hengyang 421001, Peoples R China.;[Li, Lanfang; Peng, Lijun] Univ South China, Hunan Childrens Hosp, Changsha 410007, Hunan, Peoples R China.;[Li, Lanfang; Peng, Lijun] Univ South China, Sch Pediat, Changsha 410007, Hunan, Peoples R China.;[Xu, Jin; He, Lu; Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
通讯机构：
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, China
摘要：
Autophagy is conserved in nature from lower eukaryotes to mammals and is an important self-cannibalizing, degradative process that contributes to the elimination of superfluous materials. Cardiac hypertrophy is primarily characterized by excess protein synthesis, increased cardiomyocyte size, and thickened ventricular walls and is a major risk factor that promotes arrhythmia and heart failure. In recent years, cardiomyocyte autophagy has been considered to play a role in controlling the hypertrophic response. However, the beneficial or aggravating role of cardiomyocyte autophagy in cardiac hypertrophy remains controversial. The exact mechanism of cardiomyocyte autophagy in cardiac hypertrophy requires further study. In this review, we summarize the controversies associated with autophagy in cardiac hypertrophy and provide insights into the role of autophagy in the development of cardiac hypertrophy. We conclude that future studies should emphasize the relationship between autophagy and the different stages of cardiac hypertrophy, as well as the autophagic flux and selective autophagy. Autophagy will be a potential therapeutic target for cardiac hypertrophy.
摘要：
Aim: To investigate the effect of matrine on proliferation of vascular smooth muscle cells (VSMCs) and elucidate the underlying mechanisms. Methods: Rat aortic VSMCs were cultured in medium supplemented with 10% fetal bovine serum and treated with various concentrations (0, 5, 10, 15, and 20 mg/L) of matrine for 72 h. VSMCs proliferation and cell cycle profiling were assessed using a methylene blue incorporation assay and flow cytometry, respectively. The underlying protein signaling mechanisms were determined using Western blot analysis of the expression levels of cell cycle regulatory genes, including p53, p21, p27, cyclin D1, cyclin E, cyclin-dependent kinase 2 and 4 (cdk2, cdk4), and phosphorylated Rb. The involvement of p21 and p27 pathways was further determined using small interfering RNA (siRNA) knockdown. Results: Matrine inhibited VSMC proliferation in a dose-dependent manner by promoting G1 arrest. The G1 arrest was accompanied by up-regulation of p53 and p21 protein levels, and down-regulation of cyclin D1/cdk4, cyclin E/cdk2 and phosphorylated Rb protein levels. Matrine did not affect p27 expression. Furthermore, the anti-proliferative effect of matrine was abolished by silencing of p21, but not by silencing of p27. Conclusion: Our data indicate that matrine has an inhibitory effect on VSMC proliferation via up-regulation of the p53/p21 signaling pathway and modulation of other cell cycle regulatory genes.
摘要：
The chronic unpredictable mild stress (CUMS) model is a widely used experimental model of depression. Exogenous stress-induced neuronal cell death in the hippocampus is closely associated with the pathogenesis of depression. Excessive and prolonged endoplasmic reticulum (ER) stress triggers cell death. Hydrogen sulfide (H2S), the third endogenous signaling gasotransmitter, plays an important role in brain functions as a neuromodulator and a neuroprotectant. We hypothesized that the disturbance of endogenous H2S generation and ER stress in the hippocampus might be involved in CUMS-induced depression-like behaviors. Thus, the present study focused on whether CUMS disturbs the generation of endogenous H2S and up-regulates ER stress in the hippocampus and whether exogenous H2S prevents CUMS-induced depressive-like behaviors. Results showed that CUMS-treated rats exhibit depression-like behavior and hippocampal ER stress responses including up-regulated levels of glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein, and cleaved caspase-12 expression, while the endogenous generation of H2S in the hippocampus is suppressed in CUMS-treated rats. Furthermore, exogenous H2S prevents CUMS-induced depression-like behavior. These data indicated that CUMS-induced depression-like behaviors are related to the disturbance of endogenous H2S generation and ER stress in the hippocampus and suggested that endogenous H2S and ER stress are novel treatment targets of depression.
摘要：
Objective: Human carbonic anhydrases II (CAII) gene plays an important role in different cancer. However, its relevance to gastric cancer (GC) remains unclear. In the present study, we aimed to investigate the expression of CAII in GC and explore its correlation with some clinicopathologic characteristics of GC. Methods: The expression of CAII in 20 specimens of normal gastric mucosa, 38 specimens of intraepithelial neoplasia and 112 specimens of gastric carcinoma were detected by immunohistochemical techniques. Survival in GC with CAII expression was studied. Results: The positive rate of CAII protein in normal gastric mucosa was significantly higher than that in intraepithelial neoplasia and gastric carcinoma (100% vs. 63.16% and 28.57%, P<0.001). The positive rate of CAII protein was significantly higher in gastric carcinoma at early stages than that at advanced stages (70.0% vs. 19.57%, P<0.001). The positive rate of CAII protein was significantly lower in gastric carcinoma with lymph node metastases than that without lymph node metastases (10.81% vs. 37.33%, P<0.05). Furthermore, the positive rate of CAII protein was significantly lower in poorly-differentiated gastric carcinoma than in moderately- or well-differentiated gastric carcinoma (15.94% vs. 31.03% or 60.00%, P<0.05). Moreover, CAII expression was not related with sex, age and tumor size. The patients with CAII-positive tumors showed a better survival rate than those with CAII-negative tumors (P=0.024, log-rank test). Conclusion: CAII expression was related with stages and lymph node metastases in gastric carcinoma. The reduction of CAII expression in GC might promote tumor cell motility and contribute to tumor growth and metastasis.
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：
Corticosterone, one of the glucocorticoids, is toxic to neurons and plays an important role in depressive-like behavior and depression. We previously showed that hydrogen sulfide (H2S), a novel physiological mediator, plays an inhibitory role in depression. However, the mechanism underlying H2S-triggered antidepressant-like role is not clearly known. Brain-derived neurotrophic factor (BDNF), a neurotrophic factor, plays a neuroprotective role that is mediated by its high-affinity tropomysin-related kinase B (TrkB) receptor. In this study, to investigate the underlying mechanism of H2S-induced antidepressant-like role, we explored whether H2S could protect neurons against corticosterone-mediated cyctotoxicity and whether this protective role of H2S was involved in the regulation of BDNF-TrkB pathway. Our data demonstrated that sodium hydrosulfide (NaHS), the donor of H2S, could prevent corticosterone-induced cytotoxicity, apoptosis, accumulation of intracellular reactive oxygen species (ROS) and loss of mitochondrial membrane potential (MMP) in PC12 cells. NaHS not only induced the up-regulation of BDNF but also prevented the down-regulation of BDNF by corticosterone. It was also found that blocking BDNF-TrkB pathway by K252a, an inhibitor of TrkB, abolished the protection of H2S against corticosterone-induced cytotoxicity, apoptosis, accumulation of ROS, and loss of MMP. These results suggest that H2S protects against the neurotoxicity of corticosterone by modulation of the BDNF-TrkB pathway.
作者机构：
[Chen Wu-Jun; Yin Kai; Zhao Guo-Jun; Tang Chao-Ke] Univ S China, Life Sci Res Ctr, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Chen Wu-Jun] Univ S China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Yin Kai] Univ S China, Dept Diagnost, Hengyang 421001, Peoples R China.;[Zhao Guo-Jun] Univ S China, Dept Histol & Embryol, Hengyang 421001, Peoples R China.
通讯机构：
[Tang, CK ] Univ S China, Life Sci Res Ctr, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.;Univ S China, Life Sci Res Ctr, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R 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.
