The research progress in molecular chaperones, unfolded protein response （UPR） and ER-associated degradation （ERAD） involved in the protein quality control was summarized in this paper, and then the existing probl...The research progress in molecular chaperones, unfolded protein response （UPR） and ER-associated degradation （ERAD） involved in the protein quality control was summarized in this paper, and then the existing problems and the future devel- opment prospect were also discussed. It was pointed out that the life process of protein experienced four stages including synthesizing, folding, assembling and degradation, while each stage required strict quality control. In endoplasmic reticulum （ER）, a variety of proteins had been synthesized, folded and modified to form func- tional proteins with certain conformation. When the folding was blocked in ER, the unfolded proteins would aggregate and induce the UPR, which up-regulated the level of modification enzymes folded by a series of molecular chaperones and proteins to help them accomplish folding and assembling. If these proteins were still folded incorrectly, they would enter into ERAD for being degraded.展开更多
Efficient functioning of the endoplasmic reticulum(ER) is very important for most cellular activities, such as protein folding and modification. The ER closely interacts with other organelles, including the Golgi body...Efficient functioning of the endoplasmic reticulum(ER) is very important for most cellular activities, such as protein folding and modification. The ER closely interacts with other organelles, including the Golgi body, endosome, membrane, and mitochondria, providing lipids and proteins for the repair of these organelles. ER stress can be induced by various abnormal materials in the cell. ER stress is a compensatory intracellular environment disorder that occurs during areaction. ER can sense the stress and respond to it through translational attenuation, upregulation of the genes for ER chaperones and related proteins, and degradation of unfolded proteins by a quality-control system, but excessive ER activation can cause cell death. The Pubmed and Web of Science databases were searched for full-text articles, and the terms "endoplasmic reticulum stress/unfolded protein response/gynecologic tumor cell apoptosis" were used as key words. Thirty-five studies of ER stress and unfolded protein response published from 2000 to 2016 were analyzed. Stress triggers apoptosis through a variety of signaling pathways. Increasing evidence has shown that the ER plays an important role in tumor cell diseases. The present review discusses the molecular mechanisms underlying unfolded protein response and its ability to promote survival and proliferation in gynecologic tumor cells.展开更多
The response to endoplasmic reticulum(ER)stress has been noted in both human depression cases and depression models in rodents.Wuling powder,derived from the mycelium of the esteemed fungus Xylaria Nigripes(Kl.)Sacc,h...The response to endoplasmic reticulum(ER)stress has been noted in both human depression cases and depression models in rodents.Wuling powder,derived from the mycelium of the esteemed fungus Xylaria Nigripes(Kl.)Sacc,has demonstrated efficacy in alleviating depressive symptoms.The purpose of this research was to explore the antidepressant properties of Wuling powder and its basic molecular effects,particularly regarding alterations in ER stress.A model of social defeat stress was created by introducing a mouse to the cage of an unfamiliar,hostile mouse for intervals of 5–10 min daily over a span of 10 d.Subsequently,the mice received oral doses of Wuling powder for 2 weeks.The social approach-avoidance assay was employed to evaluate signs of depression-like behaviors.Moreover,protein and gene expressions linked to ER stress triggered by social defeat were analyzed through Western blotting analysis and quantitative real-time PCR.The behavioral tests indicated that Wuling powder ameliorated behaviors associated with depression due to social defeat stress.Treatment with Wuling powder markedly reduced the increased levels of the 78-k Da glucose-regulated protein and protein disulfide isomerase caused by social defeat stress.It also diminished the expression of inositol-requiring enzyme 1α(IRE1α)and spliced X box-binding protein-1(s XBP1)at the protein and m RNA levels.Furthermore,Wuling treatment notably decreased the levels of phosphorylated eukaryotic initiation factor 2 alpha kinase(P-e IF2α),activating transcription factor 4(ATF4)and C/EBP homologous protein(CHOP),simultaneously enhancing the ratio of B-cell lymphoma 2(Bcl-2)to Bcl-2-associated X protein(Bax).These results suggested that Wuling powder could alleviate ER stress and inhibit cell apoptosis in the hippocampus by inhibiting protein translation and synthesis,thereby attenuating depressive-like behavior.展开更多
基金Supported by National Natural Science Foundation of China (Grant No.30840002,30970223)Science Foundation for Returned Chinese Scholars in Heilongjiang (Grant No.LC08C03)+3 种基金Specialized Fund for Basic Scientific Research in Higher Education Institutions of China (Grant No.DL09DA02)Scientific Research Starting Foundation for Introduced Talents in Northeast Forestry University (Grant No.015-602042)National Science Foundation for Post-doctoral Scientists of China (Grant No.200902365)Preferred Foundation of Science-Technology Program for Returned Chinese Scholars in Heilongjiang (Grant No.2009-HLJLixinLi)~~
文摘The research progress in molecular chaperones, unfolded protein response （UPR） and ER-associated degradation （ERAD） involved in the protein quality control was summarized in this paper, and then the existing problems and the future devel- opment prospect were also discussed. It was pointed out that the life process of protein experienced four stages including synthesizing, folding, assembling and degradation, while each stage required strict quality control. In endoplasmic reticulum （ER）, a variety of proteins had been synthesized, folded and modified to form func- tional proteins with certain conformation. When the folding was blocked in ER, the unfolded proteins would aggregate and induce the UPR, which up-regulated the level of modification enzymes folded by a series of molecular chaperones and proteins to help them accomplish folding and assembling. If these proteins were still folded incorrectly, they would enter into ERAD for being degraded.
文摘Efficient functioning of the endoplasmic reticulum(ER) is very important for most cellular activities, such as protein folding and modification. The ER closely interacts with other organelles, including the Golgi body, endosome, membrane, and mitochondria, providing lipids and proteins for the repair of these organelles. ER stress can be induced by various abnormal materials in the cell. ER stress is a compensatory intracellular environment disorder that occurs during areaction. ER can sense the stress and respond to it through translational attenuation, upregulation of the genes for ER chaperones and related proteins, and degradation of unfolded proteins by a quality-control system, but excessive ER activation can cause cell death. The Pubmed and Web of Science databases were searched for full-text articles, and the terms "endoplasmic reticulum stress/unfolded protein response/gynecologic tumor cell apoptosis" were used as key words. Thirty-five studies of ER stress and unfolded protein response published from 2000 to 2016 were analyzed. Stress triggers apoptosis through a variety of signaling pathways. Increasing evidence has shown that the ER plays an important role in tumor cell diseases. The present review discusses the molecular mechanisms underlying unfolded protein response and its ability to promote survival and proliferation in gynecologic tumor cells.
基金National Natural Science Foundation of China(Grant No.81100801 and 81050025)the foundation of Zhejiang Jolly Pharmaceutical Co.,Ltd.
文摘The response to endoplasmic reticulum(ER)stress has been noted in both human depression cases and depression models in rodents.Wuling powder,derived from the mycelium of the esteemed fungus Xylaria Nigripes(Kl.)Sacc,has demonstrated efficacy in alleviating depressive symptoms.The purpose of this research was to explore the antidepressant properties of Wuling powder and its basic molecular effects,particularly regarding alterations in ER stress.A model of social defeat stress was created by introducing a mouse to the cage of an unfamiliar,hostile mouse for intervals of 5–10 min daily over a span of 10 d.Subsequently,the mice received oral doses of Wuling powder for 2 weeks.The social approach-avoidance assay was employed to evaluate signs of depression-like behaviors.Moreover,protein and gene expressions linked to ER stress triggered by social defeat were analyzed through Western blotting analysis and quantitative real-time PCR.The behavioral tests indicated that Wuling powder ameliorated behaviors associated with depression due to social defeat stress.Treatment with Wuling powder markedly reduced the increased levels of the 78-k Da glucose-regulated protein and protein disulfide isomerase caused by social defeat stress.It also diminished the expression of inositol-requiring enzyme 1α(IRE1α)and spliced X box-binding protein-1(s XBP1)at the protein and m RNA levels.Furthermore,Wuling treatment notably decreased the levels of phosphorylated eukaryotic initiation factor 2 alpha kinase(P-e IF2α),activating transcription factor 4(ATF4)and C/EBP homologous protein(CHOP),simultaneously enhancing the ratio of B-cell lymphoma 2(Bcl-2)to Bcl-2-associated X protein(Bax).These results suggested that Wuling powder could alleviate ER stress and inhibit cell apoptosis in the hippocampus by inhibiting protein translation and synthesis,thereby attenuating depressive-like behavior.
