目的探讨寿命蛋白(Mortalin)在子宫内膜癌(EC)中过表达的临床病理学意义。方法采用免疫组织化学EnVision法检测Mortalin蛋白在88例EC组织和37例正常子宫内膜组织中的表达,分析其过表达与EC临床病理特征之间的关系。应用UALCAN数据库分析...目的探讨寿命蛋白(Mortalin)在子宫内膜癌(EC)中过表达的临床病理学意义。方法采用免疫组织化学EnVision法检测Mortalin蛋白在88例EC组织和37例正常子宫内膜组织中的表达,分析其过表达与EC临床病理特征之间的关系。应用UALCAN数据库分析Mortalin mRNA在EC组织中的表达水平,应用The Human Protein Atlas和The Cancer Genome Atlas(TCGA)数据库进行生存分析。结果Mortalin蛋白主要表达于EC细胞的细胞质中;在EC组织中,Mortalin蛋白的阳性率和强阳性率分别为88.6%(78/88)和56.8%(50/88),高于正常子宫内膜组织(P<0.05)。Mortalin蛋白的表达与EC患者的病理分级、TNM分期和淋巴结转移相关(P<0.05),但与年龄无关(P>0.05)。UALCAN数据库分析显示,EC组织中的Mortalin mRNA表达高于正常子宫内膜组织(P<0.05)。The Human Protein Atlas和TCGA数据库生存分析结果显示,Mortalin蛋白和mRNA高表达的EC患者总生存期低于Mortalin蛋白和mRNA低表达患者(P<0.05)。结论Mortalin的表达与EC的发生、发展及预后相关,其有望成为EC患者靶向治疗及预后评估的重要指标。展开更多
1993年,Wadhwa等[1]在小鼠胚胎成纤维细胞(mouse embryonic fibroblasts,MEF)中首次克隆出了Mortalin(mtHSP70/HSP75/Grp75/TRAP-1/PBP74),它是热休克蛋白70(heat-shock protein 70,HSP70)家族成员之一。研究表明,Mortalin参与了多种生...1993年,Wadhwa等[1]在小鼠胚胎成纤维细胞(mouse embryonic fibroblasts,MEF)中首次克隆出了Mortalin(mtHSP70/HSP75/Grp75/TRAP-1/PBP74),它是热休克蛋白70(heat-shock protein 70,HSP70)家族成员之一。研究表明,Mortalin参与了多种生理功能的调控,包括细胞存活、细胞增殖、压力应激、线粒体合成、细胞内转运等,并且可能在神经系统疾病中发挥作用。在此,本文就Mortalin的基本结构。展开更多
By controlling the proper folding of proteins imported into mitochondria and ensuring crosstalk between the reticulum and mitochondria to modulate intra cellular calcium fluxes.Mortalin is a chaperone protein that pla...By controlling the proper folding of proteins imported into mitochondria and ensuring crosstalk between the reticulum and mitochondria to modulate intra cellular calcium fluxes.Mortalin is a chaperone protein that plays crucial roles in neuronal homeostasis and activity.Howeve r,its expression and stability are strongly modified in response to cellular stresses,in particular upon alte red oxidative conditions during neurodegeneration.Here,we report and discuss the abundant literature that has highlighted its contribution to the pathophysiology of Parkinson's disease,as well as its therapeutic and prognostic potential in this still incurable pathology.展开更多
Objective:To investigate the effect of intensity-modulated radiotherapy combined with local hyperthermia on Mortalin expression in advanced liver cancer lesions and its relationship with cell proliferation and EMT.Met...Objective:To investigate the effect of intensity-modulated radiotherapy combined with local hyperthermia on Mortalin expression in advanced liver cancer lesions and its relationship with cell proliferation and EMT.Methods: A total of 82 patients with advanced liver cancer who were treated in this hospital between February 2016 and September 2017 were chosen as the research subjects, and the therapeutic regimens were reviewed and used to divide these patients into the control group (n=43) who received intensity-modulated radiotherapy and the combined treatment group (n=39) who received intensity-modulated radiotherapy combined with local hyperthermia. Abdominal puncture was done after treatment to obtain liver cancer tissue samples, and the differences in Mortalin gene, cell proliferation gene and EMT gene expression in tissues were compared.Results: After treatment, Mortalin mRNA expression in liver cancer tissues of combined treatment group was lower than that of control group;Fbxw7 mRNA expression in liver cancer tissues was higher than that of control group whereas NCX1, PRMT5 and XBP1S mRNA expression were lower than those of control group;Twist, ZEB-1, ZEB-2, Snail and HOXB7 mRNA expression in liver cancer tissues were lower than those of control group. Pearson test showed that the Mortalin gene expression in liver cancer tissues was directly correlated with cell proliferation genes and EMT genes.Conclusion:Intensity-modulated radiotherapy combined with local hyperthermia can effectively reduce Mortalin gene expression, and further optimize patients'condition by inhibiting hepatic cell proliferation, EMT activity and other pathways.展开更多
Quantum dots are the nanoparticles that are recently emerging as an alternative to organic fluorescence probes in cell biology and biomedicine,and have several predictive advantages.These include their i)broad absorpt...Quantum dots are the nanoparticles that are recently emerging as an alternative to organic fluorescence probes in cell biology and biomedicine,and have several predictive advantages.These include their i)broad absorption spectra allowing visualization with single light source,ii)exceptional photo-stability allowing long term studies and iii)narrow and symmetrical emission spectrum that is controlled by their size and material composition.These unique properties allow simultaneous excitation of different size of quantum dots with a single excitation light source,their simultaneous resolution and visualization as different colors.At present there are only a few studies that have tested quantum dots in cellular imaging.We describe here the use of quantum dots in mortalin imaging of normal and cancer cells.Mortalin staining pattern with quantum dots in both normal and cancer cells mimicked those obtained with organic florescence probes and were considerably stable.展开更多
The heat shock protein 70 family member mortalin(mot-2)/mthsp70/PBP74/GRP75 is highly expressed in cancer cells with special perinuclear cellular distribution.As a chaperon protein,mortalin has multiple subcellular lo...The heat shock protein 70 family member mortalin(mot-2)/mthsp70/PBP74/GRP75 is highly expressed in cancer cells with special perinuclear cellular distribution.As a chaperon protein,mortalin has multiple subcellular localizations and binding partners and its functions involve in mitochondria input,energy generation,intracellular trafficking,and receptor internalization.Most importantly,mortalin contributes to carcinogenesis by sequestrating key tumor suppressor p53 in the cytoplasm and inactive its transcriptional and non-transcriptional apoptotic function.The present article tries to summarize the recent findings on mortalin's role in carcinogenesis and proposes it as a potential target for cancer therapy.展开更多
Detection of circulating tumor-specific DNA, RNA or proteins can be difficult due to relative scarcity. Exosomes are extracellular vesicles, 30 - 150 nm in diameter derived from fusion of multivesicular bodies with th...Detection of circulating tumor-specific DNA, RNA or proteins can be difficult due to relative scarcity. Exosomes are extracellular vesicles, 30 - 150 nm in diameter derived from fusion of multivesicular bodies with the plasma membrane. They are composed of a lipid bilayer membrane and contain proteins, mRNA and miRNA. Exosomes are secreted by multiple cell types, including cancer cells. However, there is a relative lack of information concerning the contents of exosomes secreted by various tumor cell types. To examine exosomes in cancer, we collected blood plasma samples from patients with breast, ovarian, prostate, hepatic, gastric, colon, and pancreatic cancers. Exosomes were isolated from plasma and confirmed by AchE assay, transmission electron microscopy and expression of the CD63 exosomal marker. Expression of AFP, CA724, CA153, CEA, CA125, CA199 and PSA antigens were determined using an automated electro-chemiluminescence assay. Expression of the tumor-related chaperone protein, mortalin, was determined by Western blot analysis. Levels of exosome secretion were variable among the different tumor types. Both exosome levels and mortalin expression within tumor cell exosomes were higher than in healthy donors, except in pancreatic carcinoma, where exosomes were elevated but mortalin expression was not significantly different from healthy donors. Exosomes provide unique opportunities for the enrichment of tumor-specific materials and may be useful as biomarkers and possibly as tools of cancer therapies. Mortalin, which has been linked to cell proliferation and induction of epithelial-mesenchymal transition of cancer cells, may be useful as a prognostic biomarker and as a possible therapeutic target.展开更多
Neurodegenerative diseases are the consequences of imbalance between the production of oxidative stress and its nullification by cellular defense mechanisms. Hydrogen peroxide(H_2O_2), a precursor of deleterious react...Neurodegenerative diseases are the consequences of imbalance between the production of oxidative stress and its nullification by cellular defense mechanisms. Hydrogen peroxide(H_2O_2), a precursor of deleterious reactive oxygen species, elicits oxidative stress, resulting in severe brain injuries. Bacopa monnieri is well known for its nerve relaxing and memory enhancing properties. The present study was designed to evaluate the protective effects of extracts from Bacopa monnieri against H_2O_2 induced oxidative stress using a cellular model, neuroblastoma IMR32 cell line. The protective potential of methanolic, ethanolic, and water extracts of B. monnieri(BM-MEx, BM-EEx, and BM-WEx) was evaluated using MTT assay. Although, all the B. monnieri extracts were found to protect cells against H_2O_2-mediated stress but BM-MEx showed significantly greater protection. UPLC analysis of BM-MEx revealed various polyphenols, including quercetin, catechin, umbelliferone, and caffeic acid predominance. Further, BM-MEx was found to possess considerable greater neuroprotective potential in comparison to the standard polyphenols such as quercetin, catechin, umbelliferone, and caffeic acid. The levels of antioxidant enzymes were significantly elevated after the pretreatment of BM-MEx and quercetin. The expression levels of oxidative stress markers, such as NF200, HSP70, and mortalin, were significantly alleviated after the pretreatment of BM-MEx as shown by immunofluorescence and RT-PCR. In conclusion, the present study demonstrated the protective effects of BM-MEx, suggesting that it could be a candidate for the development of neuropathological therapeutics.展开更多
文摘目的探讨寿命蛋白(Mortalin)在子宫内膜癌(EC)中过表达的临床病理学意义。方法采用免疫组织化学EnVision法检测Mortalin蛋白在88例EC组织和37例正常子宫内膜组织中的表达,分析其过表达与EC临床病理特征之间的关系。应用UALCAN数据库分析Mortalin mRNA在EC组织中的表达水平,应用The Human Protein Atlas和The Cancer Genome Atlas(TCGA)数据库进行生存分析。结果Mortalin蛋白主要表达于EC细胞的细胞质中;在EC组织中,Mortalin蛋白的阳性率和强阳性率分别为88.6%(78/88)和56.8%(50/88),高于正常子宫内膜组织(P<0.05)。Mortalin蛋白的表达与EC患者的病理分级、TNM分期和淋巴结转移相关(P<0.05),但与年龄无关(P>0.05)。UALCAN数据库分析显示,EC组织中的Mortalin mRNA表达高于正常子宫内膜组织(P<0.05)。The Human Protein Atlas和TCGA数据库生存分析结果显示,Mortalin蛋白和mRNA高表达的EC患者总生存期低于Mortalin蛋白和mRNA低表达患者(P<0.05)。结论Mortalin的表达与EC的发生、发展及预后相关,其有望成为EC患者靶向治疗及预后评估的重要指标。
文摘1993年,Wadhwa等[1]在小鼠胚胎成纤维细胞(mouse embryonic fibroblasts,MEF)中首次克隆出了Mortalin(mtHSP70/HSP75/Grp75/TRAP-1/PBP74),它是热休克蛋白70(heat-shock protein 70,HSP70)家族成员之一。研究表明,Mortalin参与了多种生理功能的调控,包括细胞存活、细胞增殖、压力应激、线粒体合成、细胞内转运等,并且可能在神经系统疾病中发挥作用。在此,本文就Mortalin的基本结构。
文摘By controlling the proper folding of proteins imported into mitochondria and ensuring crosstalk between the reticulum and mitochondria to modulate intra cellular calcium fluxes.Mortalin is a chaperone protein that plays crucial roles in neuronal homeostasis and activity.Howeve r,its expression and stability are strongly modified in response to cellular stresses,in particular upon alte red oxidative conditions during neurodegeneration.Here,we report and discuss the abundant literature that has highlighted its contribution to the pathophysiology of Parkinson's disease,as well as its therapeutic and prognostic potential in this still incurable pathology.
文摘Objective:To investigate the effect of intensity-modulated radiotherapy combined with local hyperthermia on Mortalin expression in advanced liver cancer lesions and its relationship with cell proliferation and EMT.Methods: A total of 82 patients with advanced liver cancer who were treated in this hospital between February 2016 and September 2017 were chosen as the research subjects, and the therapeutic regimens were reviewed and used to divide these patients into the control group (n=43) who received intensity-modulated radiotherapy and the combined treatment group (n=39) who received intensity-modulated radiotherapy combined with local hyperthermia. Abdominal puncture was done after treatment to obtain liver cancer tissue samples, and the differences in Mortalin gene, cell proliferation gene and EMT gene expression in tissues were compared.Results: After treatment, Mortalin mRNA expression in liver cancer tissues of combined treatment group was lower than that of control group;Fbxw7 mRNA expression in liver cancer tissues was higher than that of control group whereas NCX1, PRMT5 and XBP1S mRNA expression were lower than those of control group;Twist, ZEB-1, ZEB-2, Snail and HOXB7 mRNA expression in liver cancer tissues were lower than those of control group. Pearson test showed that the Mortalin gene expression in liver cancer tissues was directly correlated with cell proliferation genes and EMT genes.Conclusion:Intensity-modulated radiotherapy combined with local hyperthermia can effectively reduce Mortalin gene expression, and further optimize patients'condition by inhibiting hepatic cell proliferation, EMT activity and other pathways.
文摘Quantum dots are the nanoparticles that are recently emerging as an alternative to organic fluorescence probes in cell biology and biomedicine,and have several predictive advantages.These include their i)broad absorption spectra allowing visualization with single light source,ii)exceptional photo-stability allowing long term studies and iii)narrow and symmetrical emission spectrum that is controlled by their size and material composition.These unique properties allow simultaneous excitation of different size of quantum dots with a single excitation light source,their simultaneous resolution and visualization as different colors.At present there are only a few studies that have tested quantum dots in cellular imaging.We describe here the use of quantum dots in mortalin imaging of normal and cancer cells.Mortalin staining pattern with quantum dots in both normal and cancer cells mimicked those obtained with organic florescence probes and were considerably stable.
基金Supported by Research Grants Council of Hong Kong(N-HKU718/03)National Research Foundation of Singapore(2009NRF-POC-002-097)
文摘The heat shock protein 70 family member mortalin(mot-2)/mthsp70/PBP74/GRP75 is highly expressed in cancer cells with special perinuclear cellular distribution.As a chaperon protein,mortalin has multiple subcellular localizations and binding partners and its functions involve in mitochondria input,energy generation,intracellular trafficking,and receptor internalization.Most importantly,mortalin contributes to carcinogenesis by sequestrating key tumor suppressor p53 in the cytoplasm and inactive its transcriptional and non-transcriptional apoptotic function.The present article tries to summarize the recent findings on mortalin's role in carcinogenesis and proposes it as a potential target for cancer therapy.
文摘Detection of circulating tumor-specific DNA, RNA or proteins can be difficult due to relative scarcity. Exosomes are extracellular vesicles, 30 - 150 nm in diameter derived from fusion of multivesicular bodies with the plasma membrane. They are composed of a lipid bilayer membrane and contain proteins, mRNA and miRNA. Exosomes are secreted by multiple cell types, including cancer cells. However, there is a relative lack of information concerning the contents of exosomes secreted by various tumor cell types. To examine exosomes in cancer, we collected blood plasma samples from patients with breast, ovarian, prostate, hepatic, gastric, colon, and pancreatic cancers. Exosomes were isolated from plasma and confirmed by AchE assay, transmission electron microscopy and expression of the CD63 exosomal marker. Expression of AFP, CA724, CA153, CEA, CA125, CA199 and PSA antigens were determined using an automated electro-chemiluminescence assay. Expression of the tumor-related chaperone protein, mortalin, was determined by Western blot analysis. Levels of exosome secretion were variable among the different tumor types. Both exosome levels and mortalin expression within tumor cell exosomes were higher than in healthy donors, except in pancreatic carcinoma, where exosomes were elevated but mortalin expression was not significantly different from healthy donors. Exosomes provide unique opportunities for the enrichment of tumor-specific materials and may be useful as biomarkers and possibly as tools of cancer therapies. Mortalin, which has been linked to cell proliferation and induction of epithelial-mesenchymal transition of cancer cells, may be useful as a prognostic biomarker and as a possible therapeutic target.
基金supported by grants from the Department of Science and Technology (DST), Ministry of Science and Technology, New Delhi under order No. SR/FT/LS-163 and University with Potential for Excellence (UPE) Scheme, University Grants Commission, New Delhi
文摘Neurodegenerative diseases are the consequences of imbalance between the production of oxidative stress and its nullification by cellular defense mechanisms. Hydrogen peroxide(H_2O_2), a precursor of deleterious reactive oxygen species, elicits oxidative stress, resulting in severe brain injuries. Bacopa monnieri is well known for its nerve relaxing and memory enhancing properties. The present study was designed to evaluate the protective effects of extracts from Bacopa monnieri against H_2O_2 induced oxidative stress using a cellular model, neuroblastoma IMR32 cell line. The protective potential of methanolic, ethanolic, and water extracts of B. monnieri(BM-MEx, BM-EEx, and BM-WEx) was evaluated using MTT assay. Although, all the B. monnieri extracts were found to protect cells against H_2O_2-mediated stress but BM-MEx showed significantly greater protection. UPLC analysis of BM-MEx revealed various polyphenols, including quercetin, catechin, umbelliferone, and caffeic acid predominance. Further, BM-MEx was found to possess considerable greater neuroprotective potential in comparison to the standard polyphenols such as quercetin, catechin, umbelliferone, and caffeic acid. The levels of antioxidant enzymes were significantly elevated after the pretreatment of BM-MEx and quercetin. The expression levels of oxidative stress markers, such as NF200, HSP70, and mortalin, were significantly alleviated after the pretreatment of BM-MEx as shown by immunofluorescence and RT-PCR. In conclusion, the present study demonstrated the protective effects of BM-MEx, suggesting that it could be a candidate for the development of neuropathological therapeutics.
