DJ-1/PARK7 is a gene with oncogenic potential,and its overexpression is strongly linked with the occurrence,invasion,metastasis and prognosis of numerous malignant tumors. However,the relationship between DJ-1 protein expression and the biological characteristics of non-Hodgkinlymphoma（NHL） was not previously reported in the literature.This research investigated the intracellular distribution of DJ-1 protein in NHL tissues obtained from 61 patients,finding that DJ-1 proteins located in the cytoplasm at a higher compression ratio than those in the nucleus（93.4%,72.1%,respectively）,and both were remarkably higher than those in non-tumor tissues（28.6%,14.3%,respectively）. In addition,tissue expression of DJ-1 protein is positive to the malignancy of NHL： for indolent,aggressive and highly aggressive NHL,DJ-1 protein expressing rates in the cytoplasm were 52.2%,82.9% and 100%,and in the nucleus were 82.6%、100% 和100%,respectively.The results indicate that the localization of DJ-1 protein in NHL cells may be a dynamic process,which is closely associated with development and progression of lymphoma; DJ-1 is closely related to malignant processes such as metastasis and invasion of NHL; DJ-1 is a promising NHL-related oncology biomarker.
[Gan, Runliang; Zhang, Yang; Wu, Yimou; Cheng, Ailan; Tang, Yunlian; Liu, Fang] Univ S China, Canc Res Inst, Hengyang City 421001, Hunan, Peoples R China.;[He, Rongfang] Univ S China, Dept Pathol, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.
[Gan, Runliang] Univ S China, Canc Res Inst, Hengyang City 421001, Hunan, Peoples R China.
BACKGROUND: Epstein-Barr virus (EBV) has a close association with various types of human lymphomas. Animal models are essential to elucidate the pathogenesis of human EBV-associated lymphomas. The aim of the present study is to evaluate the association between human IgG concentration and EBV-associated lymphoma development in huPBL/SCID mice. METHODS: Human peripheral blood lymphocytes (hu-PBL) from EBV-seropositive donors were inoculated intraperitoneally into SCID mouse. Immunohistochemical staining was used to examine differentiated antigens of tumor cells. EBV infection of the induced tumors was detected by in situ hybridization. IgG concentrations in the serums of 12 SCID mice were measured by unidirectional immunodiffusion assay. RESULTS: 21 out of 29 mice developed tumors in their body. Immunohistochemical staining showed that all induced tumors were LCA (leukocyte common antigen) positive, B-cell markers (CD20, CD79a) positive, and T-cell markers (both CD3 and CD45RO) negative. The tumors can be diagnosed as human B-cell lymphomas by these morphological and immunohistochemical features. In situ hybridization exhibited resultant tumor cells had EBV encoded small RNA-1 (EBER-1). Human-derived IgG could be found in the serum from SCID mice on the 15th day following hu-PBL transplantation, and IgG levels increased with the tumor development in 6 hu-PBL/SCID chimeras. CONCLUSIONS: Intraperitoneal transfer of hu-PBLs from EBV+ donors to SCID mice leads to high human IgG levels in mouse serum and B cell lymphomas. Our findings suggest that increasing levels of human-derived IgG in peripheral blood from hu-PBL/SCID mice could be used to monitor EBV-related human B-cell lymphoma development in experimental animals.
Radiation and Environmental Biophysics,2015年54(2):207-216 ISSN：0301-634X
[You, Yong; Wen, Ge-Bo; Liu, Fang] Key Laboratory of Tumor Cellular and Molecular Pathology, University of South China, College of Hunan Province, Hengyang, China;[Fang, Zhen] College of Chemistry and Materials Science, Anhui Normal University, Wuhu, China;[Wen, Ge-Bo; Lin, Ying-Wu] Laboratory of Protein Structure and Function, University of South China, Hengyang, China;[Lin, Ying-Wu; Du, Ke-Jie] School of Chemistry and Chemical Engineering, University of South China, Hengyang, China
[Wen, Ge-Bo] Univ South China, Lab Prot Struct & Funct, Hengyang 421001, Peoples R China.
Caspases - Chemical and biologicals - Death receptor pathways - Dose-dependent manner - Hepatic cells - Mitochondrial membrane potential - Signaling pathways - Transmission electron
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.
The interaction of blood glucose with heme proteins plays a key role in inducing diabetes, a serious disease threatening human health. In this study, we investigated the non-covalent interaction between glucose and myoglobin (Mb), both theoretically and experimentally, using molecular dynamics (MD) simulation combined with spectroscopic studies. It revealed that glucoses can occupy the side pocket of Mb, and bind closely to one of the xenon cavities in Mb, by hydrogen bonding interactions with two propionate groups of heme as well as surrounding amino acids. These interactions alter the conformation of the heme active site slightly and lead to an enhanced peroxidase activity of Mb, as determined by kinetic studies. This study provides general information for glucose-heme proteins interactions, and also for blood glucose-protein interactions for patients with diabetes.
背景与目的:维甲酸相关孤核受体α(retinoid acid receptor related orphan receptorα,RORα)可能参与肿瘤的调控.本实验室前期研究发现,二烯丙基二硫(diallyl disulfide,DADS)可抑制人胶质瘤U251细胞增殖,其抑制增殖作用可能与诱导RORα蛋白表达上调有关.为了明确RORα在DADS抑制人胶质瘤细胞增殖中的作用,本研究采用miRNA干扰技术抑制RORα表达,观察其对DADS抑制U251细胞增殖的影响.方法:首先将RORαmiRNA转染人胶质瘤U251细胞,运用Western blot检测转染前后RORα蛋白表达情况.实验分为未转染组,脂质体转染组和RORαmiRNA转染组及分别经30 mg/L DADS处理后的3组,共6组.MTT法检测RORα表达下调对DADS抑制胶质瘤U251细胞增殖的影响.结果: Western blot结果显示,转染RORαmiRNA细胞的RORα蛋白表达(0.09±0.05)明显低于未转染组(0.81±0.11)和脂质体转染组(0.89±0.15),其蛋白表达下调了89.5%(P<0.05).MTT结果显示,U251细胞增殖活性在RORαmiRNA转染后48 h A570值为(0.98±0.15),高于未转染组(0.47±0.11)和脂质体转染组(0.45±0.10)(P<0.05),其增殖率高达108.5%.并且RORαmiRNA转染削弱了DADS对U251细胞的增殖抑制作用,转染RORαmiRNA细胞加入DADS后的细胞增殖率(A570值为0.69±0.20)明显高于DADS处理的未转染组(0.28±0.13)和脂质体转染组(0.25±0.12)(P<0.05),其抑制率由40.4%下降为29.6%.结论:miRNA干扰RORα表达可促进U251细胞增殖,并且削弱了DADS对U251细胞的增殖抑制作用,说明RORα参与了DADS抗胶质瘤U251细胞增殖的作用