作者： Yang, Lu;Tan, Weihua;Yang, Xinzhi;You, Yong;Wang, Jing;...

期刊： JOURNAL OF CELLULAR PHYSIOLOGY,2021年236(5):3317-3335 ISSN：0021-9541

通讯作者： Wen, Gebo;Zhong, Jing

作者机构： [Wen, Gebo; Yang, Xinzhi; Zhong, Jing; Yang, Lu; Wen, GB; Zhong, J] Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.;[Wen, Gebo; Yang, Xinzhi; Zhong, Jing; Yang, Lu; Tan, Weihua] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang, Hunan, Peoples R China.;[Tan, Weihua] Univ South China, Affiliated Hosp 1, Emergency Dept, Hengyang, Hunan, Peoples R China.;[You, Yong; Wang, Jing] Univ South China, Hengyang Med Coll, Res Lab Translat Med, Hengyang, Hunan, Peoples R China.

通讯机构： [Wen, GB; Zhong, J] U;Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.

关键词： snx1 protein;snx10 protein;snx2 protein;snx27 protein;snx3 protein;snx5 protein;snx6 protein;snx9 protein;sorting nexin;tumor marker;unclassified drug;endocytosis;endosome;human;intracellular signaling;intracellular transport;malignant neoplasm;nonhuman;priority journal;protein domain;protein family;protein function;protein targeting;Review

摘要： Sorting nexins (SNXs) are a diverse group of cytoplasmic- and membrane-associated phosphoinositide-binding proteins containing the PX domain proteins. The function of SNXproteins in regulating intracellular protein trafficking consists of endocytosis, endosomal sorting, and endosomal signaling. Dysfunctions of SNXproteins are demonstrated to be involved in several cancerous/neoplastic diseases. Here, we review the accumulated evidence of the molecular structure and biological function of SNXproteinsand discuss the regulatory role of SNXproteins in distinct cancerous/neoplastic diseases. SNXfamily proteins may be a valuable potential biomarker and therapeutic strategy for diagnostics and treatment of cancerous/neoplastic diseases. © 2020 Wiley Periodicals LLC

语种： 英文

作者： Chen, Shun-Fa;Liu, Xi-Chun;Xu, Jia-Kun;Li, Lianzhi*;Lang, Jia-Jia;...

期刊： INORGANIC CHEMISTRY,2021年60(4):2839-2845 ISSN：0020-1669

通讯作者： Lin, Ying-Wu;Li, Lianzhi

作者机构： [Chen, Shun-Fa; Liu, Xi-Chun; Lin, Ying-Wu] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Xu, Jia-Kun] Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, Key Lab Sustainable Dev Polar Fisheries,Minist Ag, Lab Marine Drugs & Byprod,Pilot Natl Lab Marine S, Qingdao 266071, Peoples R China.;[Wen, Ge-Bo; Lang, Jia-Jia; Lin, Ying-Wu] Univ South China, Lab Prot Struct & Funct, Med Sch, Hengyang 421001, Peoples R China.;[Li, Lianzhi] Liaocheng Univ, Sch Chem & Chem Engn, Liaocheng 252059, Shandong, Peoples R China.

通讯机构： [Lin, Ying-Wu] U;[Li, Lianzhi] L;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;Univ South China, Lab Prot Struct & Funct, Med Sch, Hengyang 421001, Peoples R China.;Liaocheng Univ, Sch Chem & Chem Engn, Liaocheng 252059, Shandong, Peoples R China.

摘要： Protein design has received much attention in the last decades. With an additional disulfide bond to enhance the protein stability, human A15C neuroglobin (Ngb) is an ideal protein scaffold for heme enzyme design. In this study, we rationally converted A15C Ngb into a multifunctional peroxidase by replacing the heme axial His64 with an Asp residue, where Asp64 and the native Lys67 at the heme distal site were proposed to act as an acid-base catalytic couple for H2O2 activation. Kinetic studies showed that the catalytic efficiency of A15C/H64D Ngb was much higher (∼50-80-fold) than that of native dehaloperoxidase, which even exceeds (∼3-fold) that of the most efficient native horseradish peroxidase. Moreover, the dye-decolorizing peroxidase activity was also comparable to that of some native enzymes. Electron paramagnetic resonance, molecular docking, and isothermal titration calorimetry studies provided valuable information for the substrate-protein interactions. Therefore, this study presents the rational design of an efficient multifunctional peroxidase based on Ngb with potential applications such as in bioremediation for environmental sustainability. © 2021 American Chemical Society.

语种： 英文

作者： Li, Yue-yan;Zhou, Shou-hong;Chen, Shan-shan;Zhong, Jing*;Wen, Ge-bo*

期刊： Biochemical and Biophysical Research Communications,2020年524(1):77-82 ISSN：0006-291X

通讯作者： Zhong, Jing;Wen, Ge-bo

作者机构： [Zhong, J; Wen, GB; Zhong, Jing; Wen, Ge-bo; Li, Yue-yan] Univ South China, Inst Clin Med, Affiliated Hosp 1, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.;[Li, Yue-yan] Univ South China, Dept Cardiovasc Med, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Zhou, Shou-hong] Guilin Med Univ, Basic Med Coll, Dept Physiol, Guilin 541199, Guangxi, Peoples R China.;[Zhou, Shou-hong] Guilin Med Univ, Guangxi Key Lab Brain & Cognit Neurosci, Guilin 541199, Guangxi, Peoples R China.;[Chen, Shan-shan] Univ South China, Hengyang Med Coll, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Zhong, J; Wen, GB] U;Univ South China, Inst Clin Med, Affiliated Hosp 1, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.

关键词： ATP binding cassette transporter A1;Atherosclerosis;Cholesterol efflux;Foam cell;Protein arginine methyltransferase 2

摘要： Objectives: Protein arginine methyltransferase 2 (PRMT2) is closely related to the occurrence and development of atherosclerosis. However, its underlying mechanisms remain to be elucidated. The purpose of this study is to observe the effect of overexpression of PRMT2 on the formation of foam cells and to explore its possible mechanism in RAW 264.7 macrophage. Methods: Lentivirus vector of overexpression PRMT2 (LV-PRMT2) was constructed. LV-PRMT2 and lentivirus vector GV492 were transfected into RAW 264.7 macrophages, positive clone cells were screened by treatment with 4.0 μg/mL puromycin for 4 weeks. The macrophages were treated with ox-LDL (50 μg/mL) for 48 h to induce foaming. The lipid accumulation of macrophages was observed by oil red O staining. The levels of cellular total cholesterol (TC), free cholesterol (FC) and cholesteryl ester (CE) were measured by high performance liquid chromatography (HPLC) assays. The cholesterol efflux of macrophages was tested by the [3H] labeled cholesterol. The expressions of ATP binding cassette transporter A1 (ABCA1), ATP binding cassette transporter G1 (ABCG1), CD36 and scavenger receptor A1 (SR-A1) in macrophages were measured by Western Blot. Results: The results showed that LV-PRMT2 and lentivirus vector has been successfully transfected into RAW 264.7 macrophage. Compared with the Vector group, the mRNA and protein expressions of PRMT2 were significantly up-regulated (P < 0.05). Compared with Control group, the expression of PRMT2 was significantly down-regulated in ox-LDL group (P < 0.05). A large number of red lipid droplets appeared in the cells in Vector group. Compared with Vector group, lipid droplets, the levels of TC, FC and CE and CE/TC, cholesterol efflux rate and expression of ABCA1 in RAW 264.7 macrophage was significantly decreased in LV-PRMT2 group (all P < 0.05). There was no significant difference about the expressions of ABCG1, CD36 and SR-A1 between LV-PRMT2 group and Vector group (all P > 0.05). Conclusions: Overexpression of PRMT2 inhibits the formation of foam cell induced by ox-LDL in RAW 264.7 macrophage, and the mechanism may be related to the increase of ABCA1 expression and ABCA1 mediated cholesterol efflux. © 2020

语种： 英文

作者： Xia, Min;Feng, Shujun;Chen, Zuyao;Wen, Gebo;Zu, Xuyu*;...

期刊： Life Sciences,2020年250:117579 ISSN：0024-3205

通讯作者： Zu, Xuyu;Zhong, Jing

作者机构： [Chen, Zuyao; Wen, Gebo; Zhong, Jing; Zu, Xuyu; Zhong, J; Xia, Min] Univ South China, Inst Clin Med, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Zhong, Jing; Zu, Xuyu] Univ South China, Canc Res Inst, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Wen, Gebo; Xia, Min] Univ South China, Dept Endocrinol & Metab, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Feng, Shujun] Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang, Hunan, Peoples R China.

通讯机构： [Zu, XY; Zhong, J] U;Univ South China, Inst Clin Med, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.

关键词： circular ribonucleic acid;microRNA;untranslated RNA;glucose;long untranslated RNA;microRNA;untranslated RNA;aerobic glycolysis;breast cancer;down regulation;gene expression;glycolysis;human;oncogene;Review;tumor suppressor gene;upregulation;aerobic metabolism;breast tumor;female;gene expression regulation;glycolysis;metabolism;neoplasm;signal transduction;tumor cell line;Aerobiosis;Breast Neoplasms;Cell Line, Tumor;Female;Gene Expression Regulation, Neoplastic;Genes, Tumor Suppressor;Glucose;Glycolysis;Humans;MicroRNAs;Neoplasms;Oncogenes;RNA, Circular;RNA, Long Noncoding;RNA, Untranslated;Signal Transduction

摘要： Although extensive research progress has been made in breast cancer in recent years, yet the morbidity and mortality rates of breast cancer are rising, making it the major disease that endangers women's health. Energy metabolism reprogramming is featured by a state termed “aerobic glycolysis” or the Warburg effect that glycolysis is preferred even under aerobic conditions in neoplastic diseases. Widely acknowledged as an emerging hallmark in cancers, this metabolic switch shows a sophisticated role in the pathogenesis of breast cancer. The regulating effect of non-coding RNAs (ncRNAs) composed of microRNAs, long non-coding RNAs and circular RNAs is closely related to the glycolysis in breast cancer. Therefore, understand the mechanisms of ncRNAs of aerobic glycolysis in breast cancer may provide new strategy for the disease. © 2020

语种： 英文

作者： Yajun Chenx;Xianpeng Dai;Yao Yao;Jing Wang;Xinzhi Yang;...

期刊： 生物化学与生物物理学报,2019年51(3):335-337 ISSN：1672-9145

通讯作者： Gebo Wen<&wdkj&>Jing Zhong

作者机构： [Yao Yao; Zhong J.; Yang X.; Wang J.] Institute of Clinical Medicine, First Affiliated Hospital of University of South China, Hengyang, 421001, China;Department of Metabolism and Endocrinology, Second Affiliated Hospital of University of South China, Hengyang, 421001, China;[Dai X.] Department of General Surgery, Second Affiliated Hospital of University of South China, Hengyang, 421001, China;[Zhang Y.] Institute of Clinical Medicine, Second Affiliated Hospital of University of South China, Hengyang, 421001, China;Department of Metabolism and Endocrinology, First Affiliated Hospital of University of South China, Hengyang, 421001, China

通讯机构： [Gebo Wen; Jing Zhong] I;Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, China<&wdkj&>Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, China<&wdkj&>Department of Metabolism and Endocrinology, The First Affiliated Hospital of University of South China, Hengyang, China

关键词： MCF-7;apoptosis;expression;treatment;CYCLIN;can;Akt;its

摘要： Autophagy as a novel therapeutic target can inhibit or increase treatment efficacy in various types of breast cancer in a cell-type-dependent manner [1,2].Several studies have revealed that the coordination between Akt and the glycolytic pathway plays an indispensable role in mediating autophagy and caspase-dependent apoptosis,suggesting that a new regulatory mechanism for the process [3,4].Protein arginine N-methyltransferases(PRMTs)are eukaryotic enzymes that catalyze the transfer of methyl groups from S-adenosylmethionine to arginine residues of numerous PRMT substrates [5,6].PRMT2(also known as HRMT1L1)belongs to the arginine methyltransferase family [7].PRMT2β is a novel PRMT2 splice variant isolated from breast cancer cell [8].It occurs at the 3′ end of the PRMT2,resulting in loss of exons 7–9 and downstream frame-shifting [9].PRMT2β possesses 83 new amino acids at the C-terminus and its size is 301 amino acids.Our previous study reported that PRMT2β has potential antitumor effect by suppressing cyclin D1 expression [10].However,little is known about whether PRMT2β could regulate autophagy and glycolysis of MCF-7 cells.

语种： 英文

作者： Xie, Lisha;Jiang, Tao;Cheng, Ailan;Zhang, Ting;Huang, Pin;...

期刊： CURRENT MOLECULAR PHARMACOLOGY,2019年12(2):105-114 ISSN：1874-4672

通讯作者： Huang, Weiguo;Kuai, Jianke

作者机构： [Li, Pei; Zhang, Ting; Lei, Fanghong; Xie, Lisha; Cheng, Ailan; Huang, Pin; Jiang, Tao; Huang, Yun; Huang, Weiguo] Univ South China, Canc Res Inst, Hengyang Med Coll, NO28,West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wen, Gebo; Cheng, Ailan; Huang, Weiguo] Hunan Prov Key Lab Tumor Cellular & Mol Pathol 20, Hengyang 421001, Hunan, Peoples R China.;[Tang, Xia; Lin, Yunpeng; Gong, Jie] Univ South China, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.;[Kuai, Jianke] Third Hosp Xian, Dept Anesthesiol, NO10,East Sect Fengcheng 3rd Rd, Xian 710018, Shaanxi, Peoples R China.;[Xie, Lisha] Dept Yiyang Cent Hosp, Yiyang 413000, Hunan, Peoples R China.

通讯机构： [Huang, Weiguo] U;[Kuai, Jianke] T;Univ South China, Canc Res Inst, Hengyang Med Coll, NO28,West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Third Hosp Xian, Dept Anesthesiol, NO10,East Sect Fengcheng 3rd Rd, Xian 710018, Shaanxi, Peoples R China.

关键词： NPC;miR-597;14-3-3 sigma;EMT;migration;invasion

摘要： <jats:sec> <jats:title>Background:</jats:title> <jats:p>Alterations in microRNAs (miRNAs) are related to the occurrence of nasopharyngeal carcinoma (NPC) and play an important role in the molecular mechanism of NPC. Our previous studies show low expression of 14-3-3σ (SFN) is related to the metastasis and differentiation of NPC, but the underlying molecular mechanisms remain unclear.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>Through bioinformatics analysis, we find miR-597 is the preferred target miRNA of 14-3-3σ. The expression level of 14-3-3σ in NPC cell lines was detected by Western blotting. The expression of miR-597 in NPC cell lines was detected by qRT-PCR. We transfected miR-597 mimic, miR-597 inhibitor and 14-3-3σ siRNA into 6-10B cells and then verified the expression of 14-3-3σ and EMT related proteins, including E-cadherin, N-cadherin and Vimentin by western blotting. The changes of migration and invasion ability of NPC cell lines before and after transfected were determined by wound healing assay and Transwell assay.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>miR-597 expression was upregulated in NPC cell lines and repaired in related NPC cell lines, which exhibit a potent tumor-forming effect. After inhibiting the miR-597 expression, its effect on NPC cell line was obviously decreased. Moreover, 14-3-3σ acts as a tumor suppressor gene and its expression in NPC cell lines is negatively correlated with miR-597. Here 14-3-3σ was identified as a downstream target gene of miR-597, and its downregulation by miR-597 drives epithelial-mesenchymal transition (EMT) and promotes the migration and invasion of NPC.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Based on these findings, our study will provide theoretical and experimental evidences for molecular targeted therapy of NPC.</jats:p> </jats:sec>

语种： 英文

作者： Shen, Yingying;Zhong, Jing;Liu, Jianghua;Liu, Kehuang;Zhao, Jun;...

期刊： ONCOLOGY REPORTS,2018年39(6):2604-2612 ISSN：1021-335X

通讯作者： Zu, Xuyu;Cao, Renxian

作者机构： [Wen, Gebo; Zu, Xuyu; Cao, RX; Zhong, Jing; Cao, Renxian; Liu, Jianghua; Ding, Wenjun; Shen, Yingying] Univ South China, Affiliated Hosp 1, Inst Clin Med, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.;[Liu, Kehuang; Chen, Yajun; Cao, Renxian; Zeng, Ting; Zhao, Jun; Liu, Jianghua; Li, Zhimei; Xu, Ting] Univ South China, Affiliated Hosp 1, Dept Metab & Endocrinol, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Zu, XY; Cao, RX] U;Univ South China, Affiliated Hosp 1, Inst Clin Med, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.

关键词： estrogen receptor alpha;estrogen receptor alpha36;methyltransferase;mitogen activated protein kinase;phosphatidylinositol 3 kinase;PRMT2 protein;protein kinase B;tamoxifen;unclassified drug;estrogen receptor alpha;estrogen receptor alpha, human;phosphatidylinositol 3 kinase;PRMT2 protein, human;protein arginine methyltransferase;protein kinase B;signal peptide;tamoxifen;Article;breast cancer cell line;cancer growth;cancer hormone therapy;cancer resistance;controlled study;human;human cell;human tissue;MAPK signaling;MCF-7 cell line;MDA-MB-231 cell line;priority journal;protein function;protein protein interaction;breast tumor;down regulation;drug effect;drug resistance;female;gene expression regulation;metabolism;tissue microarray;tumor cell line;Breast Neoplasms;Cell Line, Tumor;Down-Regulation;Drug Resistance, Neoplasm;Estrogen Receptor alpha;Female;Gene Expression Regulation, Neoplastic;Humans;Intracellular Signaling Peptides and Proteins;MAP Kinase Signaling System;MCF-7 Cells;Phosphatidylinositol 3-Kinases;Protein-Arginine N-Methyltransferases;Proto-Oncogene Proteins c-akt;Tamoxifen;Tissue Array Analysis

摘要： Breast cancer is one of the most common malignancies in females, and 17β-estradiol (E2)/estrogen receptor α (ERα) signaling plays an important role in the initiation and progression of breast cancer. The role of the ER-α subtype and its co-regulator in the initiation of breast cancer and the occurrence of tamoxifen resistance remains to be further elucidated. In our previous studies, protein arginine N-methyltransferase 2 (PRMT2), a co-regulator of estrogen receptor-α (ER-α), was confirmed to interact with ER-α66 and has the ability to inhibit cell proliferation in breast cancer cells. In the present study, we found that tamoxifen treatment induced a decrease in PRMT2 and an increase in ER-α36 as well as ER-α36-mediated non-genomic effect in MDA-MB-231 cells, which were relatively resistant to tamoxifen by contrast to MCF-7 cells. Moreover, PRMT2 was able to interact with ER-α36 directly, suppress ER-α36 and downstream PI3K/Akt and MAPK/ERK signaling, reversing the tamoxifen resistance of breast cancer cells. The present study may be meaningful for understanding the role of PRMT2 in breast cancer progression and for developing a new endocrine therapeutic strategy for breast cancer patients with tamoxifen resistance. © 2018 Spandidos Publications. All rights reserved.

语种： 英文

作者： 康颖;文格波;姜志胜;陈熙;唐志晗;...

期刊： 西部素质教育,2018年4(1):161-162 ISSN：2095-6401

作者机构： 南华大学医学院,湖南 衡阳,421001;南华大学附属第一医院,湖南 衡阳,421001;[唐志晗; 文格波; 康颖; 姜志胜; 陈熙] 南华大学;[刘红光] 南华大学第一附属医院

关键词： 卓越医师;临床技能;教学改革

摘要： 文章从卓越医师临床技能授课团队的优化及授课方式的改革;卓越医师人文素质的培养;提高医师英语沟通能力;提升科研文献阅读能力、加强科研思路培养四个方面探讨了卓越医师临床技能教学改革。

语种： 中文

作者： Zhong, Jing;Chen, Ya-Jun;Chen, Ling;Shen, Ying-Ying;Zhang, Qing-Hai;...

期刊： ONCOLOGY REPORTS,2017年38(2):1303-1311 ISSN：1021-335X

通讯作者： Zu, Xu-Yu;Wen, Ge-Bo

作者机构： [Shen, Ying-Ying; Zhong, Jing; Wen, Ge-Bo; Zu, Xu-Yu; Wen, GB; Zhang, Qing-Hai; Cao, Ren-Xian; Chen, Ling; Chen, Ya-Jun] Univ South China, Affiliated Hosp 1, Inst Clin Med, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.;[Chen, Ya-Jun] Univ South China, Affiliated Hosp 2, Dept Metab & Endocrinol, Hengyang 421001, Hunan, Peoples R China.;[Wen, Ge-Bo; Yang, Jing; Cao, Ren-Xian] Univ South China, Affiliated Hosp 1, Dept Metab & Endocrinol, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Zu, XY; Wen, GB] U;Univ South China, Affiliated Hosp 1, Inst Clin Med, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.

关键词： androgen receptor;cyclin D1;epidermal growth factor receptor 2;estrogen receptor;glycogen synthase kinase 3beta;Ki 67 antigen;progesterone receptor;protein arginine methyltransferase;protein arginine methyltransferase 2 beta;protein kinase B;protein p53;transcription factor AP 1;unclassified drug;CCND1 protein, human;cyclin D1;epidermal growth factor receptor 2;ERBB2 protein, human;isoprotein;PRMT2 protein, human;protein arginine methyltransferase;signal peptide;tumor marker;apoptosis;Article;breast cancer;breast carcinogenesis;carboxy terminal sequence;CCND1 gene;cell count;cell proliferation;colony formation;controlled study;disease association;G1 phase cell cycle checkpoint;gene function;human;human cell;human tissue;immunoreactivity;MCF-7 cell line;priority journal;protein expression;S phase cell cycle checkpoint;signal transduction;tissue microarray;transcription initiation;transcription regulation;alternative RNA splicing;breast tumor;case control study;cell proliferation;female;gene expression regulation;genetics;metabolism;pathology;prognosis;tumor cell culture;Alternative Splicing;Apoptosis;Biomarkers, Tumor;Breast Neoplasms;Case-Control Studies;Cell Proliferation;Cyclin D1;Female;Gene Expression Regulation, Neoplastic;Humans;Intracellular Signaling Peptides and Proteins;Prognosis;Protein Isoforms;Protein-Arginine N-Methyltransferases;Receptor, ErbB-2;Tumor Cells, Cultured

摘要： Our previous study reported several alternative splicing variants of arginine N-methyltransferase 2 (PRMT2), which lose different exons in the C-terminals of the wild-type PRMT2 gene. Particularly, due to frame-shifting, PRMT2β encodes a novel amino acid sequence at the C-terminus of the protein, the function of which is not understood. In the present study, we determined the role of PRMT2β in breast cancer cell proliferation, apoptosis and its effect on the Akt signaling pathway. Stable breast cancer MCF7 cell line with lentivirus-mediated PRMT2β overexpression was obtained after selection by puromycin for 2 weeks. The effect of lentivirus-mediated PRMT2β overexpression on breast cancer cellular oncogenic properties was evaluated by MTT, colony formation, cell cycle analysis and apoptosis assays in MCF7 cells. Luciferase activity assay and western blot analysis were performed to characterize the effects of PRMT2β on cyclin D1 promoter activities and the Akt signaling pathway. Tissue microarray was performed to investigate the association of PRMT2β with breast cancer progression. Lentivirus-mediated PRMT2β overexpression suppressed the cell proliferation and colony formation of breast cancer MCF7 cells. PRMT2β overexpression induced cell cycle arrest and apoptosis of MCF7 cells. Furthermore, PRMT2β was revealed to suppress the transcription activity of the cyclin D1 promoter, and PRMT2β was also found to inhibit cyclin D1 expression via the suppression of Akt/GSK-3β signaling in breast cancer cells. Clinically, it was revealed that PRMT2β expression was negatively correlated with human epidermal growth factor receptor 2 (HER2) (p=0.033) in breast tumors. Our results revealed that PRMT2β, a novel splice variant of PRMT2, plays potential antitumor effect by suppressing cyclin D1 expression and inhibiting Akt signaling activity. This also opens a new avenue for treating breast cancer.

语种： 英文

作者： Heng Sun;Jing Zou;Ling Chen;Xuyu Zu;Gebo Wen;...

期刊： Molecular and Clinical Oncology,2017年7(6):935-942 ISSN：2049-9450

作者机构： [Gebo Wen; Jing Zhong; Heng Sun; Xuyu Zu; Ling Chen] Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China;[Gebo Wen; Heng Sun] Department of Metabolism and Endocrinology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China;[Jing Zou] Department of Neurological Medicine, Hunan Institute of Gerontology, Hunan Geriatric Hospital, Changsha, Hunan 410016, P.R. China

关键词： biological rationale;clinical issues;novel targeted therapies;obesity;prognosis;triple-negative breast cancer

摘要： Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks expression of the estrogen and progesterone receptor and does not overexpress human epidermal growth factor 2 receptor protein. TNBC is associated with special characteristics, including aggressiveness, poor prognosis and poor response to treatment, and has been attracting increasing attention worldwide. Obesity is a well-documented factor exerting a significant effect on the development of breast cancer, including TNBC. The purpose of the present review was to focus on the association between obesity and TNBC and provide a summary of novel research findings. The aim was to highlight the association between TNBC and obesity and provide an overview of novel outlooks on clinical issues, biological rationale, novel targeted therapies and prognosis, in order to draw attention to the significance of weight management, primary prevention, early diagnosis and treatment of this intractable disease.

语种： 英文

作者： Huang, Weiguo;Wang, Yafei;Zeng, Guqing;Yin, Yufang;Ouyang, Chenjie;...

期刊： TRANSLATIONAL CANCER RESEARCH,2017年6(6):1236-1247 ISSN：2218-676X

通讯作者： Cheng, Ailan

作者机构： [Li, Yu; Wang, Yafei; Cheng, Ailan; Tang, Yunlian; Ouyang, Chenjie; Huang, Weiguo] Univ South China, Canc Res Inst, Hengyang 421001, Peoples R China.;[Wen, Gebo; Huang, Weiguo] Univ South China, Postdoctoral Mobile Stn Preclin Med, Hengyang 421001, Peoples R China.;[Wang, Yafei] First Hosp Qinhuangdao, Dept Pathol, Qinhuangdao 066000, Peoples R China.;[Zeng, Guqing] Univ South China, Sch Nursing, Hengyang 421001, Peoples R China.;[Yin, Yufang] Southern Illinois Univ, Sch Med, Dept Pharmacol, Springfield, IL USA.

通讯机构： [Cheng, Ailan] U;Univ South China, Canc Res Inst, Hengyang 421001, Peoples R China.

关键词： Nasopharyngeal carcinoma (NPC);cathepsin D;interacting protein;mass spectrometry (MS);bioinformatics;invasion and metastasis

摘要： Background: Cathepsin D is a lysosomal aspartyl protease. Our previous studies have suggested that cathepsin D plays an important role in invasion and metastasis of nasopharyngeal carcinoma (NPC). Methods: To identify proteins that interact with cathepsin D and gain an insight into the role of cathepsin D in invasion and metastasis of NPC, co-immunoprecipitation (co-IP) combined with mass spectrometry (MS)-based proteomics approach was used. Cathepsin D associated proteins were identified by MS. Protein-protein interaction network were analyzed by bioinformatics including gene ontology (GO), function clustering. And co-IP and western blotting confirmation were for protein-protein interaction. The expression of cathepsin D, epidermal growth factor receptor (EGFR) and heat-shock protein 90A (HSP90A) in NPC were detected by immunohistochemistry (IHC). And the invasion and metastasis capability were detected by Transwell invasion assay. Results: One hundred and forty-one cathepsin D associated proteins were identified, including EGFR and HSP90A, proteins clearly associated with tumor invasion and metastasis. The interaction of these two proteins with cathepsin D was further validated by co-IP followed by western blotting. The 141 proteins were classified into 12 function-related groups. Protein-protein interaction network analysis indicated that cathepsin D might have a significance on invasion and metastasis of NPC by interacting with EGFR and HSP90A. Indeed, cathepsin D/EGFR/HSP90A could form complexes in NPC cells. In addition, overexpression of cathepsin D in NPC cells not only up-regulated EGFR and HSP90A, but also increased the invasive ability of NPC cells. Conclusions: Cathepsin D could enhance the invasion and metastasis capability of NPC cells may through binding to EGFR and HSP90A and triggering the activation of the signaling pathways. © Translational Cancer Research.

语种： 英文

作者： 周杰韩;吴波;左朝辉;杨叔子

期刊： 中国免疫学杂志,2016年32(12):1769-1772 ISSN：1000-484X

作者机构： [周杰韩; 吴波; 左朝辉; 杨叔子] 华中理工大学材料科学与工程学院

关键词： 盐酸吡格列酮;糖尿病肾病;TOLL受体4/MAPKs信号通路

摘要： 目的:探讨吡格列酮对糖尿病肾病大鼠肾组织中TOLL受体4 /MAPKs信号通路的影响。方法:将雄性SD随机分为对照组(n= 8)和试验组(n= 32) 。试验组SD鼠造模成功后随机分为3组进行干预,应用Western blot检测对照组和干预组大鼠肾组织中丝裂原活化蛋白激酶ERK1 /2及p38MAPK磷酸化水平。结果:与对照组比较,各组大鼠肾组织中TOLL受体4表达增强,其中ERK1 /2与JNK磷酸化水平明显升高(P<0. 05) ,但p38MAPK水平变化不明显(P>0. 05) ;与模型组比较,吡咯列酮干预组大鼠肾组织中ERK1 /2与p38MAPK磷酸化水平降低(P<0. 05) 。结论:吡格列酮通过TOLL受体4 /MAPKs / ERK1 /2与TOLL受体4 /MAPKs /JNK信号通路来完成,延缓糖尿病肾病的发生与发展。

语种： 中文

作者： 游咏;刘芳;高淑琴;林英武;文格波

期刊： 中南医学科学杂志,2016年0(5):499-503 ISSN：2095-1116

作者机构： 南华大学医学院，湖南 衡阳421001;南华大学蛋白质结构与功能实验室;南华大学化学化工学院;[格波; 高淑琴; 林英武; 刘芳; 游咏] 南华大学

关键词： 核糖;葡萄糖;肌红蛋白;非酶糖基化

摘要： 目的探讨D-核糖与D-葡萄糖对人肌红蛋白（HMb）分子构象的影响,并研究反应后晚期糖基化终末产物（AGEs）的形成情况,以期为糖尿病及其并发症的防治提供新的研究线索。方法表达、纯化获得HMb,在体外分别与D-核糖及D-葡萄糖共孵育,采用紫外可见光谱（UV-vis）监测反应后HMb的结构变化,利用荧光光谱法监测反应后AGEs的生成情况。通过SDS-PAGE观察HMb与D-核糖及D-葡萄糖反应后分子量的变化情况。结果 UV-vis显示D-核糖可在短时间内导致HMb血红素活性中心构象发生改变,且呈时间依赖性;同时随着核糖糖化时间的延长,具自发荧光的AGEs生成也逐渐增多。SDS-PAGE结果显示D-核糖能很快地与HMb发生反应,形成高分子量多聚体。而在相同的反应条件下,D-葡萄糖对HMb构象的影响及AGEs的形成显著较D-核糖为弱。结论 D-核糖,而不是D-葡萄糖,能更快速地诱导HMb发生非酶糖基化,形成AGEs。

语种： 中文

作者： Zhong, Jing;Liu, Chang;Chen, Ya-jun;Zhang, Qing-hai;Yang, Jing;...

期刊： Journal of Translational Medicine,2016年14(1):1-13 ISSN：1479-5876

通讯作者： Zu, Xu-yu;Cao, Ren-xian

作者机构： [Zu, Xu-yu; Cao, Ren-xian; Zhong, Jing; Wen, Ge-bo; Chen, Si-Rui; Zhang, Qing-hai; Kang, Xuan; Liu, Chang; Chen, Ya-jun] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang 421001, Hunan, Peoples R China.;[Liu, Chang] First Peoples Hosp Chenzhou, Dept Endocrinol & Metab, Luojiajing Rd 102, Chenzhou 423000, Hunan, Peoples R China.;[Chen, Ya-jun] Univ South China, Affiliated Hosp 2, Dept Endocrinol & Metab, Hengyang 421001, Hunan, Peoples R China.;[Wen, Ge-bo; Yang, Jing; Cao, Ren-xian] Univ South China, Affiliated Hosp 1, Dept Endocrinol & Metab, Hengyang 421001, Hunan, Peoples R China.

通讯机构： [Zu, XY; Cao, RX; Cao, Ren-xian] U;Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Endocrinol & Metab, Hengyang 421001, Hunan, Peoples R China.

关键词： S100A13;HMGA1;RNA interference;Proliferation;Invasion;Thyroid cancer

摘要： Background: S100A13 and high mobility group A (HMGA1) are known to play essential roles in the carcinogenesis and progression of cancer. However, the correlation between S100A13 and HMGA1 during cancer progression is not yet well understood. In this study, we determined the effects of S100A13 on HMGA1 expression in thyroid cancer cells and examined the role of HMGA1 in thyroid cancer progression. Methods: Stable ectopic S100A13 expression TT cellular proliferation was evaluated by nude mice xenografts assays. The effect of lentivirus-mediated S100A13 knockdown on thyroid cancer cellular oncogenic properties were evaluated by MTT, colony formation assays and transwell assays in TPC1 and SW579 cells. The effect of siRNA-mediated HMGA1 knockdown on thyroid cancer cellular proliferation and invasion were evaluated by MTT, colony formation assays and transwell assays. The tissue microarray was performed to investigate the correlation between S100A13 and HMGA1 expression in tumor tissues. Results: The ectopic expression of S100A13 could increase tumor growth in a TT cell xenograft mouse model. Moreover, lentivirus-mediated S100A13 knockdown led to the inhibition of cellular oncogenic properties in thyroid cancer cells, and HMGA1 was found to be involved in the effect of S100A13 on thyroid cancer growth and invasion. Furthermore, siRNA-mediated HMGA1 knockdown was proved to inhibit the growth of TPC1 cells and invasive abilities of SW579 cells. Clinically, it was revealed that both S100A13 and HMGA1 showed a higher expression levels in thyroid cancer cases compared with those in matched normal thyroid cases (P=0.007 and P=0.000); S100A13 and HMGA1 expressions were identified to be positively correlated (P=0.004, R=0.316) when analyzed regardless of thyroid cancer types. Conclusions: This is the first report for the association between HMGA1 and S100A13 expression in the modulation of thyroid cancer growth and invasion. Those results would provide an essential insight into the effect of S100A13 on carcinogenesis of thyroid tumor, rending S100A13 to be potential biological marker for the diagnosis of thyroid cancer. © 2016 Zhong et al.

语种： 英文

作者： Zuo, Jianhong;Wen, Juan;Lei, Mingsheng;Wen, Meiling;Li, Sai;...

期刊： Medical Oncology,2016年33(2):1-9 ISSN：1357-0560

通讯作者： Luo, Zhaoyang;Wen, Gebo

作者机构： [Wen, Gebo; Zuo, Jianhong; Luo, Zhaoyang; Wen, GB; Lv, Xiu; Li, Sai; Wen, Juan] Univ South China, Sch Med, Hengyang 421001, Hunan, Peoples R China.;[Zuo, Jianhong; Lv, Xiu; Wen, Meiling; Li, Sai] Univ South China, Nanhua Hosp, Hengyang 421000, Hunan, Peoples R China.;[Lei, Mingsheng] Zhangjiajie City Hosp, Dept Resp & Crit Care Med, Zhangjiajie 427000, Hunan, Peoples R China.

通讯机构： [Luo, ZY; Wen, GB] U;Univ South China, Sch Med, Hengyang 421001, Hunan, Peoples R China.

关键词： beta actin;glucose transporter 1;hypoxia inducible factor 1alpha;nerve cell adhesion molecule;uvomorulin;vimentin;cadherin;CDH2 protein, human;glucose transporter 1;leukocyte antigen;SLC2A1 protein, human;vimentin;Article;cancer patient;cancer prognosis;cancer staging;cell migration;controlled study;epithelial mesenchymal transition;human;human cell;human tissue;hypoxia;immunohistochemistry;larynx cancer;larynx carcinoma;larynx squamous cell carcinoma;lymph node metastasis;priority journal;protein expression;survival rate;survival time;tumor invasion;Western blotting;aged;cell hypoxia;cell motion;larynx tumor;lymph node metastasis;metabolism;middle aged;mortality;pathology;physiology;squamous cell carcinoma;tumor cell culture;Aged;Antigens, CD;Cadherins;Cell Hypoxia;Cell Movement;Epithelial-Mesenchymal Transition;Glucose Transporter Type 1;Humans;Laryngeal Neoplasms;Lymphatic Metastasis;Middle Aged;Neoplasms, Squamous Cell;Survival Rate;Tumor Cells, Cultured;Vimentin

摘要： The purpose of this study is to explore the role of hypoxia on the invasion and metastasis of laryngeal carcinoma. The invasion and migration ability of laryngeal cancer SCC10A cell was detected by transwell assay. Western blot was applied to analyze the expression of EMT-related proteins. Fifty-seven samples from postoperative patients with laryngeal cancer were collected to study. Immunohistochemistry was used to examine the expression of GLUT-1 and EMT-related proteins (Vim, E-cad, N-cad) in normal laryngeal squamous epithelial tissue, laryngeal cancer adjacent tissues and laryngeal squamous cell carcinoma tissues. Hypoxia promoted laryngeal cancer cell invasion and migration. Hypoxia also enhanced the expression of GLUT-1, vimentin and N-cad, which exist statistically significant correlation with the clinical staging and lymph node metastases (P<0.05). The expression of GLUT-1 is positively correlated with Vim and N-cad expression in laryngeal squamous cell carcinoma tissues, but negatively correlated with E-cad expression. The patient survival rate with the positive expression of GLUT-1, Vim and N-cad becomes much shorter compared with those with negative expression of GLUT-1, Vim and N-cad (P<0.05). Hypoxia promoted laryngeal cancer cell invasion and migration via EMT. © 2016, Springer Science+Business Media New York.

语种： 英文

作者： 聂鑫;余益本;文格波

期刊： 中国免疫学杂志,2016年32(12):1769-1772 ISSN：1000-484X

作者机构： 湖北医药学院附属东风医院老年病科, 十堰, 442000;南华大学病原生物学重点实验室, 衡阳, 421001;南华大学国家临床医学研究中心, 衡阳, 421001;[聂鑫] 湖北医药学院附属东风医院老年病科, 十堰, 442000;[余益本] 南华大学病原生物学重点实验室, 衡阳, 421001

关键词： 盐酸吡格列酮;糖尿病肾病;TOLL受体4/MAPKs信号通路

摘要： 目的:探讨吡格列酮对糖尿病肾病大鼠肾组织中TOLL受体4 /MAPKs信号通路的影响。方法:将雄性SD随机分为对照组(n= 8)和试验组(n= 32) 。试验组SD鼠造模成功后随机分为3组进行干预,应用Western blot检测对照组和干预组大鼠肾组织中丝裂原活化蛋白激酶ERK1 /2及p38MAPK磷酸化水平。结果:与对照组比较,各组大鼠肾组织中TOLL受体4表达增强,其中ERK1 /2与JNK磷酸化水平明显升高(P<0. 05) ,但p38MAPK水平变化不明显(P>0. 05) ;与模型组比较,吡咯列酮干预组大鼠肾组织中ERK1 /2与p38MAPK磷酸化水平降低(P<0. 05) 。结论:吡格列酮通过TOLL受体4 /MAPKs / ERK1 /2与TOLL受体4 /MAPKs /JNK信号通路来完成,延缓糖尿病肾病的发生与发展。

语种： 中文

作者： 陈亚军;钟警;杨靖;文格波

期刊： 中华疾病控制杂志,2015年19(5):458-461 ISSN：1674-3679

作者机构： [陈亚军] 南华大学附属第二医院内分泌科;[钟警; 杨靖; 文格波] 南华大学附属第一医院临床医学研究所;南华大学医学院病理生理学教研室

关键词： 基因表达;剪接体;乳腺肿瘤

摘要： 目的检测并观察蛋白质精氨酸甲基转移酶2(protein arginine methyltransferase 2,PRMT2)及其新的剪接体PRMT2α、PRMT2β、PRMT2γ在雌激素受体α(estrogen receptor α,ERα)阳性和ERα阴性乳腺癌细胞株中的表达情况。方法提取ERα阳性乳腺癌细胞株(ZR-75-l、BT474、T47D、MCF-7)和ERα阴性的乳腺癌细胞株(MDA-MB-453、SK-BR-3、MDA-MB-231)总RNA并用RT-PCR方法检测PRMT2及其新剪接体mRNA的表达,采用内对照甘油醛-3-磷酸脱氢酶(glyceraldehyde-3-phosphate dehydrogenase,GAPDH)同时进行相对定量以进行校正。结果不同乳腺癌细胞株中均可检测到PRMT2及其新剪接体的表达,在ERα阳性乳腺癌细胞株(ZR-75-1、BT474、T47D、MCF-7)中表达均较高,而在ERα阴性的乳腺癌细胞株(MDA-MB453、SK-BR-3、MDA-MB-231)中表达均较低。结论PRMT2与PRMT2α、PRMT2β、PRMT2γ基因在不同乳腺癌细胞株中存在差异表达,在ERα阴性乳腺癌细胞中低于ERα阳性乳腺癌细胞,PRMT2各剪接体有可能和PRMT2一样通过ERα信号途径影响乳腺癌的发生发展。

语种： 中文

作者： 张新华;唐志晗;文格波;吴移谋

期刊： 山西科技,2015年30(3):117-118,129 ISSN：1004-6429

作者机构： 南华大学医学院,湖南衡阳,421001;南华大学党政办公室,湖南衡阳,421001;[唐志晗; 文格波; 吴移谋; 张新华] 南华大学

关键词： 卓越计划;医教协同机制;临床医学

摘要： 在基础医学与临床医学紧密结合基础上探索构建医教协同机制,有利于保障卓越医生教育培养计划的高效实施。从程序协同、目标协同、主体协同和制度协同等方面,探讨了支撑卓越计划实施的医教协同机制的构建。

语种： 中文

作者： Zu, Xuyu;Zhong, Jing;Tan, Jingjing;Tan, Li;Yang, Dong;...

期刊： INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,2015年35(3):693-701 ISSN：1107-3756

通讯作者： Jiang, Yuyang

作者机构： [Wen, Gebo; Zhong, Jing; Cao, Renxian; Tan, Jingjing; Tan, Li; Liu, Jianghua; Yang, Dong; Zu, Xuyu; Ding, Wenjun; Zhang, Qinghai; Liu, Wen] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Yuyang] Tsinghua Univ, Grad Sch Shenzhen, Guangdong Prov Key Lab Chem Biol, Shenzhen 518055, Guangdong, Peoples R China.;[Jiang, Yuyang] Tsinghua Univ, Grad Sch Shenzhen, Guangdong Prov Key Lab Chem Biol, 2279 Lishui Rd, Shenzhen 518055, Guangdong, Peoples R China.

通讯机构： [Jiang, Yuyang] T;Tsinghua Univ, Grad Sch Shenzhen, Guangdong Prov Key Lab Chem Biol, 2279 Lishui Rd, Shenzhen 518055, Guangdong, Peoples R China.

关键词： 2 morpholino 8 phenylchromone;epidermal growth factor receptor 2;high mobility group A1a protein;phosphatidylinositol 3 kinase;protein kinase B;transcription factor Sp1;transforming growth factor beta1;wortmannin;high mobility group A protein;phosphatidylinositol 3 kinase;protein kinase B;transforming growth factor beta1;Article;binding affinity;breast cancer cell line;breast carcinoma;cancer growth;cell invasion;cell migration;cell proliferation;controlled study;gel mobility shift assay;gene expression;human;human cell;immunofluorescence;immunofluorescence test;luciferase assay;lymph node metastasis;major clinical study;priority journal;promoter region;protein expression;quantitative analysis;real time polymerase chain reaction;reverse transcription polymerase chain reaction;signal transduction;tissue microarray;upregulation;adult;aged;breast tumor;cancer grading;cancer staging;cell motion;drug effects;female;gene expression regulation;genetics;metabolism;middle aged;pathology;signal transduction;transcription initiation;tumor cell line;tumor volume;Adult;Aged;Breast Neoplasms;Cell Line, Tumor;Cell Movement;Cell Proliferation;Female;Gene Expression Regulation, Neoplastic;HMGA Proteins;Humans;Middle Aged;Neoplasm Grading;Neoplasm Staging;Phosphatidylinositol 3-Kinases;Promoter Regions, Genetic;Proto-Oncogene Proteins c-akt;Signal Transduction;Transcriptional Activation;Transforming Growth Factor beta1;Tumor Burden

摘要： Transforming growth factor-β1 (TGF-β1) signaling and high mobility group A (HMGA1) are known to play essential roles in the progression of breast cancer by inducing epithelial-mesenchymal transition. However, the correlation between TGF-β1 and HMGA1 in breast cancer cell is not yet well understood. In this study, we determined the effects of TGF-β1 on HMGA1 expression in breast cancer cells and examined the role of HMGA1 in breast cancer progression. Our results demonstrated that TGF-β1 induced the expression of HMGA1 in both MCF-7 and MDA-MB-231 breast cancer cells, as shown by RT-qPCR and immunofluorescence staining; however, the TGF-β1-induced expression of HMGA was blocked by treatment of the cells with phosphatidylinositol-3 kinase (PI3K) signaling inhibitors. Moreover, the HMGA1 promoter activity was found to be activated by TGF-β1 in the MCF-7 and MDA-MB-231 cells and we found that specificity protein 1 (Sp1) was involved in the TGF-β1-induced HMGA1 promoter activity, as shown by luciferase activity assay. Furthermore, the enforced expression of HMGA1 by transfection with a HMGA1 promoter enhanced cellular oncogenic properties, including proliferation, migration and invasion, and a tissue microarray revealed that breast tumors expressing human epidermal growth factor receptor 2 (HER2) showed higher expression levels of HMGA1 (P=0.007). In addition, higher HMGA1 expression levels were also observed in the ductal breast cancer cases compared with the lobular breast cancer cases (P=0.000). These findings establish the first link between HMGA1 and TGF-β1 in breast cancer, providing further evidence of the pivotal role of HMGA1 in breast cancer progression.

语种： 英文

作者： Liu, Fang;Du, Ke-Jie;Fang, Zhen;You, Yong;Wen, Ge-Bo*;...

期刊： Radiation and Environmental Biophysics,2015年54(2):207-216 ISSN：0301-634X

通讯作者： Wen, Ge-Bo

作者机构： [Wen, Ge-Bo; You, Yong; Liu, Fang] Univ South China, Key Lab Tumor Cellular & Mol Pathol, Coll Hunan Prov, Hengyang 421001, Peoples R China.;[Lin, Ying-Wu; Du, Ke-Jie] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Fang, Zhen] Anhui Normal Univ, Coll Chem & Mat Sci, Wuhu 241000, Peoples R China.;[Wen, Ge-Bo; Lin, Ying-Wu] Univ South China, Lab Prot Struct & Funct, Hengyang 421001, Peoples R China.

通讯机构： [Wen, Ge-Bo] U;Univ South China, Lab Prot Struct & Funct, Hengyang 421001, Peoples R China.

关键词： Uranium;Hepatic cell;Cytotoxicity;Apoptosis;Caspases

摘要： Ur anium release into the environment is a threat to human health, and the mechanisms of cytotoxicity caused by uranium are not well-understood. To improve our understanding in this respect, we herein evaluated the effects of uranium exposure on normal rat hepatic BRL cells. As revealed by scanning electron microscopy and transmission electron microscope analysis, uranyl nitrate was found to be transformed into uranyl phosphate particles in the medium and taken up by BRL cells in an endocytotic uptake manner, which presumably initiates apoptosis of the cell, although soluble uranyl ion may also be toxic. The apoptosis of BRL cells upon uranium exposure was also confirmed by both the acridine orange and ethidium bromide double staining assay and the Annexin V/propidium iodide double staining assay. Further studies revealed that uranium induced the loss of mitochondrial membrane potential in a dose-dependent manner. Moreover, the uranium-induced apoptosis was found to be associated with the activation of caspase-3, caspase-8 and caspase-9, indicating both a mitochondria-dependent signaling pathway and a death receptor pathway by a crosstalk. This study provides new chemical and biological insights into the mechanism of uranium toxicity toward hepatic cells, which will help seek approaches for biological remediation of uranium.

语种： 英文