期刊：
FRONTIERS IN IMMUNOLOGY,2018年9(NOV):2735 ISSN：1664-3224
通讯作者：
Li, Liuzhe
作者机构：
[Gorny, Miroslaw K.; Li, Liuzhe] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.;[Liu, Yan] Univ South China, Inst Pathogen Biol, Med Coll, Hengyang, Peoples R China.
通讯机构：
[Li, Liuzhe] N;NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
作者机构：
[Zhou, Xiaoqing; Liu, Yunhai; Li, Zhibin; Xia, Jian; Yang, Qidong; Yu, Fang; Zeng, Sian] Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;[Zhan, Qiong] Cent S Univ, Xiangya Hosp 2, Dept Neurol, Changsha 410011, Hunan, Peoples R China.;[Yuan, Mei] Univ South China, Affiliated Hosp 2, Dept Neurol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Xia, Jian] C;Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.
摘要：
Background and aims: microRNA223 (miR-223) plays an important role in the development of atherosclerosis and ischemic stroke. It is involved in regulation of multiple physiological and pathophysiological processes such as cholesterol metabolism, endothelial cell (EC) function, and thrombosis. Here we investigated the role of methylation regulation of MIR-223 promoter region in atherosclerotic cerebral infarction (ACI) patients. Methods: A total of 23 patients with ACI and 32 healthy individuals were recruited. We performed bisulfite sequencing PCR and real-time PCR to detect methylation levels of MIR-223 promoter region and miR-223, respectively, in genomic DNA isolated from peripheral blood leukocytes. Results: Mean methylation levels of a total of nine CpGs of MIR-223 promoter were significantly lower in ACI patients than in healthy individuals (p < 0.01), and were also significantly lower in individuals with carotid atherosclerosis than those without carotid atherosclerosis (p < 0.05). Meanwhile, miR-223 expression in leukocytes was significantly higher in ACI patients than in healthy individuals (p < 0.05). miR-223 level was negatively correlated with mean methylation levels of MIR-223 promoter (r = -0.4451, p < 0.01). The methylation level of MIR-223 promoter revealed a positive correlation with the circulating total cholesterol level (r = 0.318, p = 0.019). Conclusions: Hypomethylation of MIR-223 promoter is associated with atherosclerotic cerebral infarction. (C) 2017 Published by Elsevier Ireland Ltd.
期刊：
Lipids in Health and Disease,2017年16(1):1-10 ISSN：1476-511X
通讯作者：
Wang, Zuo;Zhang, Hai
作者机构：
[Ma, Xiaofeng] Univ South China, Dept Cardiol, Affiliated Nanhua Hosp, Hengyang 421001, Peoples R China.;[Qu, Kai; Ma, Xiaofeng; Liu, Yami; Wang, Zuo] Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Human Prov, Hengyang 421001, Peoples R China.;[Tan, Yanmei] Changde Vocat Tech Coll, Dept Pathol, Changde 415000, Peoples R China.;[He, Xinglan] Women & Children Healthcare Hosp Zhu Zhou, Zhuzhou 412000, Peoples R China.;[Zhang, Hai] Univ South China, Dept Pathol, Affiliated Hosp 1, Hengyang 421001, Peoples R China.
通讯机构：
[Wang, Zuo; Zhang, Hai] U;Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Human Prov, Hengyang 421001, Peoples R China.;Univ South China, Dept Pathol, Affiliated Hosp 1, Hengyang 421001, Peoples R China.
关键词：
Lipoprotein(a);Apolipoprotein(a);Diallyl disulfide;Extracellular regulated protein kinases;Mitogen-activated protein kinases;HepG2 cell
摘要：
Lipoprotein(a) [LP(a)] is implicated as a common and independent risk factor for cardiovascular diseases. The therapeutic options currently available for reducing plasma LP(a) concentrations are limited. Diallyl disulphide (DADS), the main component of garlic, regulates lipid metabolism in hepatocytes and adipocytes through ERK1/2 signalling. This study aimed to assess the effect of DADS on apolipoprotein(a) [apo(a)] in HepG2 cells. We also determined the effects of DADS on apo(a) expression and secretion in HepG2 cells as well as the underlying mechanisms. We examined the role of DADS on apo(a) expression in HepG2 cells by treating cell with different concentrations of DADS (10, 20, 40 and 80 μg/mL) for 24 h or treating cells with 40 μg/mL DADS for 0, 6, 12, 24 and 48 h. Then we used quantitative real-time PCR to analysis apo(a) mRNA levels, used Western blot to analysis apo(a) protein levels and used enzyme-linked immunosorbent assay to test apo(a) secreted levels. To farther determined the role of DADS, we applied Transfection of small interfering RNA to knockdown ELK-1levels and applied PD98059, a specific inhibitor of ERK1/2, to block ERK1/2 signal. The results show DADS inhibited apo(a) at both the mRNA and protein levels in HepG2 cells in a dose-dependent manner. DADS-mediated inhibition of apoa(a) expression in HepG2 cells was attenuated when the cells were cultured in medium containing PD98059 (ERK1/2 inhibitor) or were transfected with siRNAs against MEK1 or ELK-1. Overexpression of apo(a) yielded similar results. This study reveals that DADS can downregulate apo(a) expression in a dose-dependent manner via the MEK-ERK12-ELK-1 pathway.
摘要：
Cardiovascular disease is a growing major global public health problem. Oxidative stress is regarded as one of the key regulators of pathological physiology, which eventually leads to cardiovascular disease. However, mechanisms by which FGF-2 rescues cells from oxidative stress damage in cardiovascular disease is not fully elucidated. Herein this study was designed to investigate the protective effects of FGF-2 in H2O2-induced apoptosis of H9c2 cardiomyocytes, as well as the possible signaling pathway involved. Apoptosis of H9c2 cardiomyocytes was induced by H2O2 and assessed using methyl thiazolyl tetrazolium assay, Hoechst, and TUNEL staining. Cells were pretreated with PI3K/Akt inhibitor LY294002 to investigate the possible PI3K/Akt pathways involved in the protection of FGF-2. The levels of p-Akt, p-FoxO3a, and Bim were detected by immunoblotting. Stimulation with H2O2 decreased the phosphorylation of Akt and FoxO3a, and induced nuclear localization of FoxO3a and apoptosis of H9c2 cells. These effects of H2O2 were abrogated by pretreatment with FGF-2. Furthermore, the protective effects of FGF-2 were abolished by PI3K/Akt inhibitor LY294002. In conclusion, our data suggest that FGF-2 protects against H2O2-induced apoptosis of H9c2 cardiomyocytes via activation of the PI3K/Akt/FoxO3a pathway.
摘要：
The pathogenesis of Chlamydia-induced inflammation is poorly understood. pORF5 is the only secreted protein encoded by Chlamydial plasmid. This study aims to investigate the effects of pORF5 on the production of interleukin-1 beta (IL-1 beta) and interleukin-18 (IL-18) and the underlying mechanisms of these effects. THP-1 (a human acute monocytic leukemia cell line) cells were stimulated by pORF5 with or without pretreatment with Natch domain, Leucine-rich repeat and PYD-containing protein 3 (NALP3) siRNA, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) siRNA, cysteine aspartate-specific protease-1 (caspase-1) specific inhibitor and p38 mitogen-activated protein kinase (p38 MAPK) inhibitor. IL-1 beta, IL-18 and caspase-1 expression was detected through both ELISA and qRT-PCR. NALP3 and ASC expression was detected by qRT-PCR. The expression of caspase-1 and phosphorylated-p38 MAPK was detected by western blot analysis. pORF5 induced IL-1 beta, IL-18, caspase-1 and NALP3 inflammasome expression in THP-1 cells. Caspase-1 inhibitor significantly reduced pORF5-induced IL-1 beta and IL-18 expression. The siRNAs for NALP3 inflammasome significantly reduced pORF5-induced IL-1 beta, IL-18 and caspase-1 expression. Furthermore, p38 MAPK inhibitor significantly reduced pORF5-induced IL-1 beta, IL-18, caspase-1 and NALP3 inflammasome expression. pORF5 could induce production of IL-1 beta and IL-18 via NALP3 inflammasome activation and p38MAPK pathway. pORF5 protein might play an important role in Chlamydia pathogenesis. This study provides a new insight into the molecular pathogenesis of Chlamydial diseases.
