作者机构：
[刘恩岐; 李海鹏] First People's Hospital of Chenzhou, University of South China, Chenzhou, Hunan, 423000, China;[江高峰] Institute of Drug and Pharmacology, University of South China, Hengyang Hunan, 421001, China;Xiangnan University, Chenzhou Hunan, 423000, China;[李琼] Xi'an Jiaotong University, Medical College, Xi'an, 710061, China;[郭立军] First People's Hospital of Chenzhou, University of South China, Chenzhou, Hunan, 423000, China, Xiangnan University, Chenzhou Hunan, 423000, China
摘要：
Doxorubicin (DOX) is a potent and available antitumor therapeutic agent; however, its clinical application is limited due to its cardiotoxicity. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOX-induced cardiotoxicity. Therefore, the aim of the present study was to investigate whether the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway is involved in the cardioprotection of H2S against DOX-induced cardiotoxicity. The present study demonstrated that pretreatment with sodium hydrosulfide (NaHS; a donor of H2S) prior to DOX exposure attenuated the decreased cell viability, the increased apoptosis rate and the intracellular accumulation of reactive oxygen species (ROS) in H9c2 cardiac myocytes. Exposure of H9c2 cardiac myocytes to DOX upregulated the expression levels of phosphorylated ERK1/2, which had been reduced by pretreatment with NaHS or N-acetyl-L-cysteine, a ROS scavenger. In addition, H2S upregulated the anti-apoptotic protein, Bcl-2 and downregulated the pro-apoptotic protein, Bax. Notably, U0126, a selective inhibitor of ERK1/2, was observed to mimic the above-mentioned cytoprotective activity of H2S. In conclusion, these findings indicate that H(2)5 attenuates DOX-induced cardiotoxicity by inhibiting ROS-mediated activation of ERK1/2 in H9c2 cardiac myocytes.
关键词：
Endothelin-1;High mobility group box 1;Bronchial epithelial cells;Endothelin A receptor;Focal adhesion kinase;Acute lung injury;Acute respiratory distress syndrome
摘要：
Both endothelin-1 (ET-1) and high mobility group box 1 (HMGB1) reportedly are closely involved in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). In this study, we explored the regulatory effects of ET-1 on the expression of HMGB1 in human bronchial epithelial cells (HBEpCs). Primary HBEpCs were treated with ET-1 with or without transcription inhibitor actinomycin D, ETA receptor blocker BQ123, ETB receptor blocker BQ788, focal adhesion kinase (FAK) inhibitor or shRNA, or different kinase inhibitors. ET-1 increased the HMGB1 mRNA level in a statistically significant dose- and time-dependent manner within 8 hours of treatment, which was reflected in the dose-dependent induction of the HMGB1 protein level and the FAK activity. BQ123 and FAK inhibitor or shRNA, but not BQ788, completely abolished the promoting effect of ET-1 on the expression of HMGB1. Luciferase reporter assays revealed that neither ET-1 nor ETA nor FAK inhibition had any significant effect on the HMGB1 gene promoter activity. In the presence of the transcription inhibitor actinomycin D, the HMGB1 mRNA level markedly decreased over time, and ET-1 dose-dependently rescued the HMGB1 mRNA level. This effect of ET-1 was completely abolished by BQ123 and FAK inhibitor or shRNA, but not by BQ788. In conclusion, this study provides the first evidence that ET-1 upregulates the expression of HMGB1 in HBEpCs by increasing the stability of HMGB1 mRNA via the ETA receptor by a FAK-dependent mechanism. It adds new insights into the molecular mechanisms underlying ALI/ARDS.
摘要：
A new chemosensor 7-nitro-2,1,3-benzoxadiazole-4-allyl-N-(thiophen-2-ylmethyl)carbamate (NBDTC) was synthesized and utilized for palladium detection based on the Tsuji-Trost reaction. NBDTC displayed specific and ratiometric fluorescent responses toward palladium species. The chemosensor showed more than 50-fold enhancement in fluorescence intensity with the presence of PEG400 and palladium because NBDTC can be transformed to NBDT under palladium-catalyzing Tsuji-Trost reaction. NBDTC displayed high selectivity and sensitivity for palladium species with the detection limit of 1.13 x 10(-9) M. (C) 2015 Elsevier B.V. All rights reserved.
摘要：
Doxorubicin (DOX) is a potent and currently available antitumor therapeutic agent; however, its clinical application is limited by the occurrence of cardiotoxicity. Preliminary evidence indicates that hydrogen sulfide (H2S) may exert protective effects against DOX cardiotoxicity. Therefore, the aim of the present study was to investigate whether calreticulin (CRT) is involved in the cardioprotection of H2S against DOX-induced cardiotoxicity. DOX was observed to markedly induce injuries, including cytotoxicity and apoptosis, and also enhance the expression level of CRT. Notably, pretreatment of H9c2 cells with sodium hydrosulfide (a donor of H2S) significantly attenuated the decreased cell viability, the increased apoptosis rate and the increased expression level of CRT in H9c2 cells. In addition, pretreatment of H9c2 cells with N-acetyl-L-cysteine, a scavenger of reactive oxygen species (ROS) prior to exposure to DOX, markedly decreased the expression of CRT. These results indicate that exogenous H2S attenuates DOX-induced cardiotoxicity by inhibiting CRT expression in H9c2 cardiac cells.
摘要：
Preclinical evaluation of the anti-neoplastic activity of antisense oligonucleotide (AS) suppression of human insulin-like growth factor I receptor (IGF-IR) in human epithelial ovarian cancer (EOC). Ovarian cancer cells from 36 patients with EOC were investigated under serum-free tissue culture conditions. IGF-I production was evaluated by standard ELISA. IGF-IR and phosphorylated IRS-1, AKT, and MAP kinase expression and protein levels were evaluated by immunohistochemistry and Western blotting. Cancer cell growth and proliferation assays were performed in triplicates using MTT assay. Apoptosis was evaluated by TUNNEL assay. All ovarian cancer tissue samples tested produced IGF-I and expressed IGF-IR, supporting the existence of an autocrine loop. Treatment of primary ovarian cancer cell lines with an IGF-1R AS inhibited growth and proliferation and decreased clonogenicity in soft agar assay. AS treatment was demonstrated to inhibit the expression of IGF-1R and decrease the concentration of phosphorylated IRS-1, AKT, and MAP kinase signaling protein downstream of the IGF-IR. We also observed that the IGF-1R AS sensitized cancer cell lines to cisplatin in vitro through the PI3K pathway. IGF-IR enhances the proliferation and tumorigenicity of human ovarian cancer cells and inhibition of IGF-IR by AS oligonucleotide treatment potentiates the activity of cisplatin in vitro. Therefore, IGF-1R is a potential molecular target in ovarian cancer.
作者机构：
[陈根; 林杰; 秦旭平] Institute of Drug and Pharmacology, University of South China, Hengyang 421001, China;[李洁] The First People's Hospital of Chenzhou, Chenzhou 423000, China;[王俊杰] Xiang Nan University, Chenzhou 423000, China;[周楠] Medical College, Xi 'an Jiaotong University, Xi 'an 710061, China
通讯机构：
Institute of Drug and Pharmacology, University of South China, China
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.
期刊：
Biochemical and Biophysical Research Communications,2010年391(4):1693-1697 ISSN：0006-291X
通讯作者：
Luo, Di-xian
作者机构：
[Liao, Duan-fang; Xia, Chenglai; Luo, Di-xian; Li, Junmo; Wang, Chun; Xu, Canxin; Zhu, Bingyang] Univ S China, Res Ctr Life Sci, Inst Pharm & Pharmacol, Div Pharmacoproteom, Hengyang 421001, Hunan, Peoples R China.;[Hu, Zhuowei] Peking Union Med Coll, Beijing 100730, Peoples R China.;[Hu, Zhuowei] Chinese Acad Med Sci, Inst Mat Med, Beijing 100730, Peoples R China.;[Luo, Di-xian] First Peoples Hosp Chenzhou City, Chenzhou 421001, Hunan, Peoples R China.;[Xiong, Yan; Luo, Di-xian] Cent S Univ, Sch Pharmaceut, Dept Pharmacol, Changsha 410083, Hunan, Peoples R China.
通讯机构：
[Luo, Di-xian] U;Univ S China, Res Ctr Life Sci, Inst Pharm & Pharmacol, Div Pharmacoproteom, Hengyang 421001, Hunan, Peoples R China.
