作者机构：
[Jiang, Yue; Peng, Xiao-Shan; Ren, Kun; Shi, Jin-Feng; Yi, Guang-Hui; Tang, Zhen-Li] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Shi, Jin-Feng; Mo, Zhong-Cheng] Univ South China, Dept Histol & Embryol, Hengyang 421001, Hunan, Peoples R China.;[Liu, Xing] Chinese Acad Med Sci, Inst Basic Med Sci, Sch Basic Med, Natl Lab Med Mol Biol,Peking Union Med Coll, Beijing 100005, Peoples R China.;[Zhang, Qing-Hai] Univ South China, Affiliated Hosp 1, Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Yi, Guang-Hui] U;Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
ApoM;TGF-β;TAK-1;JNK;C-Jun
摘要：
Apolipoprotein M (apoM) is a relatively novel apolipoprotein that plays pivotal roles in many dyslipidemia-associated diseases; however, its regulatory mechanisms are poorly understood. Many cytokines have been identified that down-regulate apoM expression in HepG2 cells, among which transforming growth factor-β (TGF-β) exerts the most potent effects. In addition, c-Jun, a member of the activated protein 1 (AP-1) family whose activity is modulated by c-Jun N-terminal kinase (JNK), decreases apoM expression at the transcriptional level by binding to the regulatory element in the proximal apoM promoter. In this study, we investigated the molecular mechanisms through which TGF-β decreases the apoM level in HepG2 cells. The results revealed that TGF-β inhibited apoM expression at both the mRNA and protein levels in a dose- and time-dependent manner and that it suppressed apoM secretion. These effects were attenuated by treatment of cells with either SP600125 (JNK inhibitor) or c-Jun siRNA. 5Z-7-oxozeaenol [(a TGF-β-activated kinase 1 (TAK-1) inhibitor)] also attenuated the TGF-β-mediated inhibition of apoM expression and suppressed the activation of JNK and c-Jun. These results have demonstrated that TGF-β suppresses apoM expression through the TAK-1-JNK-c-Jun pathway in HepG2 cells.
作者机构：
[Tang, Dan; Ou, Weiwei; Wang, Deming; Chen, Quan; Wang, Jiazheng; Xiao, Ji] Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Peoples R China.;[Mo, Zhongcheng] Univ South China, Dept Histol & Embryol, Hengyang 421001, Peoples R China.;[Tang, Chaoke] Univ South China, Inst Cardiovasc Res, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Peng, Liangyu] Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Peoples R China.
通讯机构：
[Wang, Deming; Peng, Liangyu] U;Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Peoples R China.
关键词：
liver X receptor;cytokine;mRNA decay;tristetraprolin;mitogen-activated protein kinase
摘要：
Liver X receptors (LXRs) have anti-inflammatory properties. Whether LXRs play a role in post-transcriptional control of inflammatory cytokine expression is not clear. Here, we firstly identified that the synthetic LXR agonist T0901317 promoted IL-1β, IL-6 and TNFa mRNA degradation. Moreover, T0901317 destabilized TNFa mRNA through its 3'-untranslated region. In addition, T0901317 increased the expression of tristetraprolin (TTP), while antagonizing TTP with siRNA abrogated T0901317-mediated inflammatory cytokine mRNA decay. Interestingly, T0901317 repressed LPS-induced phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK) in THP-1 macrophages. The evidence presented here confirms that LXR activation with T0901317 inhibits the phosphorylation of ERK1/2 and p38 MAPK, likely resulting in the increased expression of TTP and the decay of LPS-induce inflammatory cytokine mRNAs.
通讯机构：
[Tang, Shengsong] H;[Tang, Shengsong] U;Hunan Univ Med, Biomed Res Ctr, Huaihua 418000, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Dept Histol & Embryol, Hengyang 421001, Peoples R China.
关键词：
Macrophage colony-stimulating factor;chemoresistance;apoptosis;autophagy;breast cancer
摘要：
Macrophage colony-stimulating factor is a vital factor in maintaining the biological function of monocyte–macrophage lineage. It is expressed in many tumor tissues and cancer cells. Recent findings indicate that macrophage colony-stimulating factor might contribute to chemoresistance, but the precise mechanisms are unclear. This study was to explore the effect of macrophage colony-stimulating factor on doxorubicin resistance in MCF-7 breast cancer cells and the possible mechanism. In the study, the human breast cancer cells, MCF-7, were transfected with macrophage colony-stimulating factor. We document that cytoplasmic macrophage colony-stimulating factor induces doxorubicin resistance and inhibits apoptosis in MCF-7 cells. Further studies demonstrated that cytoplasmic macrophage colony-stimulating factor-mediated apoptosis inhibition was dependent on the activation of PI3K/Akt/Survivin pathway. More importantly, we found that macrophage colony-stimulating factor-induced autophagic cell death in doxorubicin-treated MCF-7 cells. Taken together, we show for the first time that macrophage colony-stimulating factor-induced doxorubicin resistance is associated with the changes in cell death response with defective apoptosis and promotion of autophagic cell death.
作者机构：
[朱明燕; 郑翔; 石金凤; 彭凤玲; 欧含笑] Department of Histology and Embryology, University of South China, Hengyang 421001, China;[朱明燕; Zeng, Gao-Feng] Department of Cardiovascular Medicine, the Second Affiliated Hospital of University of South China, Hengyang 421001, China;[王毓] Department of Anesthesiology, the Second Affiliated Hospital of University of South China, Hengyang 421001, China;[王燕] Department of Clinical Laboratory, the Second Affiliated Hospital of University of South China, Hengyang 421001, China;[莫中成] Department of Histology and Embryology, University of South China, Hengyang 421001, China. zhchmo@hotmail.com
关键词：
B类I型清道夫受体;血清淀粉样蛋白A;p38丝裂原活化蛋白激酶;动脉粥样硬化
摘要：
为探讨血清淀粉样蛋白A (serum amyloid A, SAA)对巨噬细胞B类I型清道夫受体(scavenger receptor class B type I, SR-BI)的表达以及炎症反应的影响及分子机制,采用SAA、p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase, p38-MAPK)激动剂anisomycin或抑制剂SB203580处理THP-1巨噬细胞,以实时定量PCR、Western blot和ELISA分别检测细胞中SR-BI、炎症因子及磷酸化p38-MAPK的表达。结果显示,与对照组相比,SAA处理THP-1细胞后,SR-BI的表达下调,而炎症因子与磷酸化p38蛋白的表达则上调,且这种效应呈浓度和时间依赖性(P < 0.05)。与SAA单独处理组比较,SAA与p38- MAPK激动剂anisomycin共孵育细胞后,细胞SR-BI表达下调,炎症因子及磷酸化p38蛋白表达增加(P < 0.05);而SAA与p38- MAPK抑制剂SB203580共同处理细胞后,细胞SR-BI表达增加,炎症因子及磷酸化p38蛋白表达减少(P < 0.05)。结果提示, SAA可促进THP-1巨噬细胞炎症反应,其机制与p38-MAPK的磷酸化及SR-BI表达的下调有关。
期刊：
Journal of Physiology and Biochemistry,2016年72(4):657-667 ISSN：1138-7548
通讯作者：
Yi, Guang-Hui
作者机构：
[Jiang, Yue; Peng, Xiao-Shan; Liu, Xing; Ren, Kun; Yi, Guang-Hui; Suo, Rong; Tang, Zhen-Li] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, 28 W Changsheng Rd, Hengyang City 421001, Hunan, Peoples R China.;[Xiong, Sheng-Lin] You Country Peoples Hosp, Zhuzhou 412300, Hunan, Peoples R China.;[Zhang, Qing-Hai] Univ South China, Affiliated Hosp 1, Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Mo, Zhong-Cheng] Univ South China, Inst Cardiovasc Res, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Yi, Guang-Hui] U;Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, 28 W Changsheng Rd, Hengyang City 421001, Hunan, Peoples R China.
关键词：
S1P;SR-BI;ABCA1;SphK;S1P receptors;Release
摘要：
Sphingosine-1-phosphate (S1P), which has emerged as a pivotal signaling mediator that participates in the regulation of multiple cellular processes, is derived from various cells, including vascular endothelial cells. S1P accumulates in lipoproteins, especially HDL, and the majority of free plasma S1P is bound to HDL. We hypothesized that HDL-associated S1P is released through mechanisms associated with the HDL maturation process. ApoA-I, a major HDL apolipoprotein, is a critical factor for nascent HDL formation and lipid trafficking via ABCA1. Moreover, apoA-I is capable of promoting bidirectional lipid movement through SR-BI. In the present study, we confirmed that apoA-I can facilitate the production and release of S1P by HUVECs. Furthermore, we demonstrated that ERK1/2 and SphK activation induced by apoA-I is involved in the release of S1P from HUVECs. Inhibitor and siRNA experiments showed that ABCA1 and SR-BI are required for S1P release and ERK1/2 phosphorylation induced by apoA-I. However, the effects triggered by apoA-I were not suppressed by inhibiting ABCA1/JAK2 or the SR-BI/Src pathway. S1P released due to apoA-I activation can stimulate the (ERK1/2)/SphK1 pathway through S1PR (S1P receptor) 1/3. These results indicated that apoA-I not only promotes S1P release through ABCA1 and SR-BI but also indirectly activates the (ERK1/2)/SphK1 pathway by releasing S1P to trigger their receptors. In conclusion, we suggest that release of S1P induced by apoA-I from endothelial cells through ABCA1 and SR-BI is a self-positive-feedback process: apoA-I-(ABCA1 and SR-BI)-(S1P release)-S1PR-ERK1/2-SphK1-(S1P production)-(more S1P release induced by apoA-I).
作者机构：
[Wu, Jian-Feng; He, Ping-Ping; Shi, Jin-Feng; Ouyang, Xin-Ping; Mo, Zhong-Cheng; Peng, Juan; Liu, Dan; Lv, Yun-Cheng; Tang, Chao-Ke; Xie, Wei; Tang, Yan-Yan; Yao, Feng; Tang, CK] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res,Med Res Ctr, Hengyang 421001, Hunan, Peoples R China.;[Tang, Xiang-Yang; Wan, Wei; Lv, Yun-Cheng] Univ South China, Lab Clin Anat, Hengyang 421001, Peoples R China.;[Tang, Yan-Yan] Cent S Univ, Key Lab Carcinogenesis, Chinese Minist Hlth, Changsha 410013, Hunan, Peoples R China.;[Tang, Yan-Yan] Cent S Univ, Key Lab Carcinogenesis & Canc Invas, Chinese Minist Educ, Canc Res Inst, Changsha 410013, Hunan, Peoples R China.;[Zhang, Ping] Hunan Univ Sci & Engn, Sch Elect & Informat Engn, Yongzhou 425100, Hunan, Peoples R China.
通讯机构：
[Ouyang, XP; Tang, CK] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res,Med Res Ctr, Hengyang 421001, Hunan, Peoples R China.
关键词：
DNA methylation;Macrophages;Cholesterol;Atherosclerosis;Aorta;Gene expression;Lipids;Epigenetics
摘要：
ATP-binding cassette transporter A1 (ABCA1) plays a critical role in maintaining cellular cholesterol homeostasis. The purpose of this study is to identify the molecular mechanism(s) underlying ABCA1 epigenetic modification and determine its potential impact on ABCA1 expression in macrophage-derived foam cell formation and atherosclerosis development. DNA methylation induced foam cell formation from macrophages and promoted atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Bioinformatics analyses revealed a large CpG island (CGI) located in the promoter region of ABCA1. Histone methyltransferase enhancer of zeste homolog 2 (EZH2) downregulated ABCA1 mRNA and protein expression in THP-1 and RAW264.7 macrophage-derived foam cells. Pharmacological inhibition of DNA methyltransferase 1 (DNMT1) with 5-Aza-dC or knockdown of DNMT1 prevented the downregulation of macrophage ABCA1 expression, suggesting a role of DNA methylation in ABCA1 expression. Polycomb protein EZH2 induced DNMT1 expression and methyl-CpG-binding protein-2 (MeCP2) recruitment, and stimulated the binding of DNMT1 and MeCP2 to ABCA1 promoter, thereby promoting ABCA1 gene DNA methylation and atherosclerosis. Knockdown of DNMT1 inhibited EZH2-induced downregulation of ABCA1 in macrophages. Conversely, EZH2 overexpression stimulated DNMT1-induced ABCA1 gene promoter methylation and atherosclerosis. EZH2-induced downregulation of ABCA1 gene expression promotes foam cell formation and the development of atherosclerosis by DNA methylation of ABCA1 gene promoter.
