摘要：
Transcriptional coactivator PPAR gamma coactivator-1 alpha (PGC-1 alpha) and corepressor receptor-interacting protein 140 (RIP140) are opposing-functional regulators in maintaining energy balance of most metabolic tissues and cells. However, the relative contributions of both factors to energy metabolism in cardiomyocytes remain largely unknown. Herein, we reported that the relative protein levels of RIP140/PGC-1 alpha were up-regulated in the failing hearts after chronic myocardial infarction (MI), and correlated negatively with the energy state index phosphocreatine (PCr)/ATP ratios. Real-time PCR analysis revealed that mRNA expressions of estrogen related receptor alpha (ERR alpha), peroxisome proliferate activated receptor alpha and beta (PPAR alpha, PPAR beta), nuclear respiratory factor 1 (NRF1) and their target genes were repressed by RIP140 and induced by PGC-1 alpha in a dose dependent manner in neonatal rat cardiomyocytes. We also observed that overexpression of RIP140 through adenovirus delivery can abrogate the PGC-1 alpha-mediated induction of mitochondrial membrane potential elevation and mitochondrial biogenesis, and activate both autophagy and apoptosis pathways. We conclude that RIP140 and PGC-1 alpha exert antagonistic role in regulating cardiac energy state and mitochondrial biogenesis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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：
[Ji, Xiaoying] Laboratory of Molecular Medicine, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China;Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan 421001, China;[Li, Ping] Nanjing Maternity and Child Health Hospital, Affiliated Hospital of Nanjing Medical University, Nanjing 210004, China;[He, Nongyue] State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China;[Sirois, Pierre] IPS Therapeutique Inc., Sherbrooke, QC J1E 4K8, Canada
通讯机构：
[Li, K.] L;Laboratory of Molecular Medicine, College of Pharmaceutical Science, Soochow University, China
摘要：
Aim:we aim at measurement enhanced effect of oxidized lipoprotien(a) [oxLp(a)] on permeability of monolayer endothelial cells and relationship with reactive oxygen species( ROS) generation and desmogleins(DSGs) expression.Methods and Results:Trans-endothelial permeability was assayed by transwell and reactive oxygen species(ROS) was determined by DCFH-DA staining.RT-PCR was carried out to determine DSG1 and DSC2 expression in mRNA,respectively.Trans-endothelial permeability was enhanced by oxLP(a) dose and time dependently.The most marked effect appeared at a concentration of 100 mg/L,Trans-endothelial permeability reached the maximum value after 2 h of FITC-dextran addition,and then gradually decreased after 4 h.oxLp(a) induces the generation of cellular reactive oxygen species (ROS),and this effect could be inhibited by superoxide dismutase(SOD).Incubation of HUVECs with oxLp(a) resulted in a dose and time-dependent down-regulation of DSG1 and DSC2 expression at transcriptional level.Conclusion: permeability of monolayer endothelial cells was enhanced by oxLp(a) and it is related to up-regulating ROS formation and down-regulating desmogleins expression.
摘要：
AIM: Apolipoprotein A-I (apoA-I), the major component of high-density lipoprotein (HDL), has been recently found to suppress inflammation. This study was to investigate the effects and potential mechanisms of apoA-I on the CD40/CD40 ligand (CD40L) proinflammatory signaling pathway. METHODS: Human THP-1 macrophage-derived foam cells were treated with sCD40L alone or in the presence of apoA-I. Secretion of proinflammatory cytokines was performed by enzyme-linked immunosorbent assay(ELISA). The proteins and mRNA expression were examined by western-blot and real-time PCR analysis, respectly. Cholesterol efflux was assessed by liquid scintillation counting. Cholesterol depletion of macrophages was performed with methylated beta-cyclodextrin. RESULTS: ApoA-I inhibits the inflammatory response stimulated by soluble CD40L (sCD40L) in macrophages. In addition, apoA-I inhibited the sCD40L-stimulated activation of nuclear factor-kB (NF-kB). The apoA-I-induced NF-kB deactivation was related to the decreased recruitment of tumor necrosis factor receptor-associated factor 6 (TRAF-6), a crucial adapter protein for CD40 in macrophages, to lipid rafts after being treated by sCD40L. When interfering the expression of ATP-binding cassette transporter A1 (ABCA1), a major cholesterol transporter for apoA-I in macrophages, it could significantly diminish the effect of apoA-I on the sCD40L-stimulated inflammatory response. CONCLUSION: ApoA-I suppresses CD40 proinflammatory signaling in macrophages by preventing TRAF-6 translocation to lipid rafts through ABCA1-dependent regulation of free cholesterol (FC) efflux, which may present a novel mechanism of apoA-I-mediated inflammation inhibition in macrophages.
通讯机构：
[Tang, Chao-Ke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.
关键词：
ATP-binding cassette transporter A1;Interleukin-12;Interleukin-18;Liver X receptor alpha;Nuclear factor-kappa B
摘要：
Background: Interleukin (IL)-18 and IL-12 synergize for the production of interferon (IFN)-γ, which can downregulate ATP-binding cassette transporter A1 (ABCA1) expression. The aim of the present study was to investigate the effect of IL-18 and/or IL-12 on ABCA1 expression. Methods and Results: IL-18 combined with IL-12 decreased ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells, whereas IL-18 or IL-12 alone had no effect. IL-12 increased IL-18 receptor (IL-18R) expression, which was suppressed by small interfering RNA (siRNA) for signal transducer and activator of transcription 3. IL-18R but not IL-12 receptor siRNA completely reversed the effects of IL-18 and IL-12 on ABCA1 expression and cellular cholesterol efflux. Treatment with IL-18 plus IL-12 markedly augmented nuclear translocation of nuclear factor (NF)-κB but had no effect on expression and activity of liver X receptor α. IL-18 and IL-12 also significantly increased zinc finger protein 202 (ZNF202) levels and IFN-γ secretion. Furthermore, siRNA for ZNF202 or IFN-γ significantly impaired IL-18/IL-12-induced suppression of ABCA1, whereas NF-κB siRNA treatment blocked IL-18/IL-12' action on ZNF202 levels, IFN-γ secretion, and ABCA1 expression. Conclusions: IL-18 and IL-12 together can decrease ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells through the IL-18R/NF-κB signaling pathway.
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.
期刊：
Asian Pacific Journal of Cancer Prevention,2012年13(3):1053-1057 ISSN：1513-7368
通讯作者：
He, Zhi-Wei
作者机构：
[He, Zhi-Wei; Lu, Yan; Li, Bin-Bin; Huang, Guo-Liang; Liu, Xing-Yan] Guangdong Med Coll, Sinoamer Canc Res Inst, Dongguan, Peoples R China.;[Liu, Ou-Fei; Guo, Hong-Qiang] Zhengzhou Univ, Affiliated Canc Hosp, Zhengzhou, Peoples R China.;[Yang, Feng] Univ S China, Dept Pharm & Life Sci, Hengyang, Peoples R China.
通讯机构：
[He, Zhi-Wei] G;Guangdong Med Coll, Sinoamer Canc Res Inst, Dongguan, Peoples R China.
关键词：
ATF1;coloretal cancer;prognosis
摘要：
Objective: Identifying cancer-related genes or proteins is critical in preventing and controlling colorectal cancer (CRC). This study was to investigate the clinicopathological and prognostic value of activating transcription factor 1 (ATF1) in CRC. Methods: Protein expression of ATF1 was detected using immunohistochemistry in 66 CRC tissues. Clinicopathological association of ATF1 in CRC was analyzed with chi-square test or Fisher's exact test. The prognostic value of ATF1 in CRC is estimated using the Kaplan-Meier analysis and Cox regression models. Results: The ATF1 protein expression was significantly lower in tumor tissues than corresponding normal tissues (51.5% and 71.1%, respectively, P = 0.038). No correlation was found between ATF1 expression and the investigated clinicopathological parameters, including gender, age, depth of invasion, lymph node status, metastasis, pathological stage, vascular tumoral emboli, peritumoral deposits, chemotherapy and original tumor site (all with P > 0.05). Patients with higher ATF1 expression levels have a significantly higher survival rate than that with lower expression (P = 0.026 for overall survival, P = 0.008 for progress free survival). Multivariate Cox regression model revealed that ATF1 expression and depth of invasion were the predictors of the overall survival (P = 0.008 and P = 0.028) and progress free survival (P = 0.002 and P = 0.005) in CRC. Conclusions: Higher ATF1 expression is a predictor of a favorable outcome for the overall survival and progress free survival in CRC.
作者机构：
[唐国华; 孙少卫] Research Center of Life Science, South China University, Hengyang, 421001, China;[赵强] Department of Pathology, First Affiliated Hospital, South China University, Hengyang, 421001, China;[贺修胜] Cancer Research Institute of Medical College, South China University, Hengyang, 421001, China
通讯机构：
[Tang, G.-H.] R;Research Center of Life Science, South China University, Hengyang, China
摘要：
Termites are an extremely successful group of wood-degrading organisms and are therefore important both for their roles in carbon turnover in the environment and as potential sources of biochemical catalysts for efforts aimed at converting wood into biofuels. To contribute to the evolutional study of termite digestive symbiosis, a bacterial 16S rRNA gene clone library from the gut microbial community of the fungus-growing termite Macrotermes barneyi was constructed. After screening by restriction fragment length polymorphism (RFLP) analysis, 25 out of 105 clones with unique RFLP patters were sequenced and phylogenetically analyzed. Many of the clones (95%) were derived from three phyla within the domain bacteria: Bacteroidetes, Firmicutes and Proteobacteria. In addition, a few clones derived from Deferribacteres, Actinobacteria and Planctomycetes were also found. No one clone affiliated with the phylum Spirochaetes was identified, in contrast to the case of wood-feeding termites. The phylogenetic analysis revealed that nearly half of the representative clones (11 phylotypes) formed monophyletic clusters with clones obtained from other termite species, especially with the sequences retrieved from fungus-growing termites. These results indicate that the presence of termite-specific bacterial lineages implies a coevolutional relationship of gut microbes and host termites. The remaining 14 clones formed a cluster, and there was very low sequence similarity (30 to 40%) to known 16S rRNA sequences. The 16S rRNA gene sequence data showed that the majority of the intestinal microflora of M. barneyi consisted of new, uncultured species previously unknown to microbiologists.
作者机构：
[Shuhua Cui; Qinhui Tuo; DuanFang Liao] Learning Key Laboratory for Pharmacoproteomics,School of Life Science and Technology,University of South China;[Shuhua Cui; Qinhui Tuo; DuanFang Liao] Department of Traditional Chinese Diagnotics,School of Pharmacy,Hunan University of Chinese Medicine
会议名称：
第11届全国脂质与脂蛋白学术会议
会议时间：
2012-09-21
会议地点：
太原
会议论文集名称：
第11届全国脂质与脂蛋白学术会议论文集
摘要：
<正>Objective:The aim of the present study was to determine the effect of Daxx on apoptosis of RAW264.7 cells induced by Chol.MpCD. Methods:The eukaryotic vector of Daxx was constructed to be stably tr
