Cell protection from stresses by heat shock protein (HSP) was previously attributed to its ability to prevent aggregation and to accelerate refolding of damaged proteins. It plays an important role in cell survival af...Cell protection from stresses by heat shock protein (HSP) was previously attributed to its ability to prevent aggregation and to accelerate refolding of damaged proteins. It plays an important role in cell survival after extremely harsh protein damaging treatment leading to necrotic cell death. On the other hand, protein repair function of HSP cannot explain how it protects cell from stresses which do not cause direct protein damage. These stresses kill cell through activation of apoptotic program. Recently it has been found that HSP can meditate suppression of a stress-activated protein kinase, JNK, an early component of stress-induced apoptotic signaling pathway.These observations can provide a basis for HSP’s function of anti-apoptosis.展开更多
Severe fever with thrombocytopenia syndrome(SFTS)caused by the SFTS virus(SFTSV)is an emerging disease in East Asia with a fatality rate of up to 30%.However,the viral-host interaction of SFTSV remains largely unknown...Severe fever with thrombocytopenia syndrome(SFTS)caused by the SFTS virus(SFTSV)is an emerging disease in East Asia with a fatality rate of up to 30%.However,the viral-host interaction of SFTSV remains largely unknown.The heat-shock protein 90(Hsp90)family consists of highly conserved chaperones that fold and remodel proteins and has a broad impact on the infection of many viruses.Here,we showed that Hsp90 is an important host factor involved in SFTSV infection.Hsp90 inhibitors significantly reduced SFTSV replication,viral protein expression,and the formation of inclusion bodies consisting of nonstructural proteins(NSs).Among viral proteins,NSs appeared to be the most reduced when Hsp90 inhibitors were used,and further analysis showed that their translation was affected.Co-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90βspecifically interacted with them.Knockdown of Hsp90βexpression also inhibited replication of SFTSV.These results suggest that Hsp90βplays a critical role during SFTSV infection and could be a potential target for the development of drugs against SFTS.展开更多
The metabolic enzyme CTP synthase(CTPS) is able to compartmentalize into filaments,termed cytoophidia,in a variety of organisms including bacteria,budding yeast,fission yeast,fruit flies and mammals.A previous study i...The metabolic enzyme CTP synthase(CTPS) is able to compartmentalize into filaments,termed cytoophidia,in a variety of organisms including bacteria,budding yeast,fission yeast,fruit flies and mammals.A previous study in budding yeast shows that the filament-forming process of CTPS is not sensitive to temperature shift.Here we study CTPS filamentation in the fission yeast Schizosaccharomyces pombe.To our surprise,we find that both the length and the occurrence of cytoophidia in S.pombe decrease upon cold shock or heat shock.The temperature-dependent changes of cytoophidia are fast and reversible.Taking advantage of yeast genetics,we demonstrate that heat-shock proteins are required for cytoophidium assembly in S.pombe.Temperature sensitivity of cytoophidia makes S.pombe an attractive model system for future investigations of this novel membraneless organelle.展开更多
Photothermal therapy(PTT)has shown promising applications in tumor therapies.However,due to laserinduced nonspecific heating and heat diffusion,high levels of hyperthermia(>50℃)in tumor tissues often increase the ...Photothermal therapy(PTT)has shown promising applications in tumor therapies.However,due to laserinduced nonspecific heating and heat diffusion,high levels of hyperthermia(>50℃)in tumor tissues often increase the risk of cancer recurrence and metastasis,which causes the patient pain and destroys the surrounding normal cells and tissues.It is therefore important to develop photothermal strategies that have excellent therapeutic efficiencies under low-temperature conditions(≤45℃).In addition,the heterogeneity and complexity of tumors require the development of combinatorial antitumor treatments as the therapeutic efficiency of monomodal PTT is not currently sufficient.Herein,we have adopted a stepwise synthetic approach to develop a highly efficient multimodal therapeutic agent GA@PCOF@PDA by successive bonding defect functionalization(BDF),guest encapsulation,and surface modification steps.The covalently grafted porphyrinic photosensitizers(Por),encapsulated gambogic acid(GA),and surface-modified PDA film are independently responsible for photodynamic therapy(PDT),heat-shock protein 90(HSP90)down-regulation and chemotherapy(CT),and low-temperature PTT.This proof-ofconcept study illustrates an efficient,generalized approach to design high-performance covalent organic framework(COF)-based nanoagents that can be easily tailored to combine different therapeutic modalities for improved cancer theranostics at low temperatures.展开更多
In the present study, we examined the effect of oxygen glucose deprivation（OGD） post-conditioning（PostC） on neural cell apoptosis in OGD-PostC model and the protective effect on primary cortical neurons against OG...In the present study, we examined the effect of oxygen glucose deprivation（OGD） post-conditioning（PostC） on neural cell apoptosis in OGD-PostC model and the protective effect on primary cortical neurons against OGD injury in vitro. Four-h OGD was induced by OGD by using a specialized and humidified chamber. To initiate OGD, culture medium was replaced with de-oxygenated and glucose-free extracellular solution-Locke＇s medium. After OGD treatment for 4 h, cells were then allowed to recover for 6 h or 20 h. Then lactate dehydrogenase（LDH） release assay, Western blotting and flow cytometry were used to detect cell death, protein levels and apoptotic cells, respectively. For the PostC treatment, three cycles of 15-min OGD, followed by 15 min normal cultivation, were applied immediately after injurious 4-h OGD. Cells were then allowed to recover for 6 h or 20 h, and cell death was assessed by LDH release assay. Apoptotic cells were flow cytometrically evaluated after 4-h OGD, followed by re-oxygenation for 20 h（O4/R20）. In addition, Western blotting was used to examine the expression of heat-shock protein 70（HSP70）, Bcl-2 and Bax. The ratio of Bcl-2 expression was（0.44±0.08）% and（0.76±0.10）%, and that of Bax expression was（0.51±0.05）% and（0.39±0.04）%, and that of HSP70 was（0.42±0.031）% and（0.72±0.045）% respectively in OGD group and PostC group. After O4/R6, the rate of neuron death in PostC group and OGD groups was（28.96±3.03）% and（37.02±4.47）%, respectively. Therefore, the PostC treatment could up-regulate the expression of HSP70 and Bcl-2, but down-regulate Bax expression. As compared with OGD group, OGD-induced neuron death and apoptosis were significantly decreased in PostC group（P0.05）. These findings suggest that PostC inhibited OGD-induced neuron death. This neuro-protective effect is likely achieved by anti-apoptotic mechanisms and is associated with over-expression of HSP70.展开更多
目的:探讨热休克蛋白27(heat shock protein 27,HSP27)在胃癌、癌旁正常胃黏膜组织和慢性胃炎中的蛋白及其mRNA的表达情况,为HSP27应用于临床胃良恶性病变的鉴别诊断提供实验依据。方法:采用组织芯片技术检测病理诊断明确的34例胃癌患...目的:探讨热休克蛋白27(heat shock protein 27,HSP27)在胃癌、癌旁正常胃黏膜组织和慢性胃炎中的蛋白及其mRNA的表达情况,为HSP27应用于临床胃良恶性病变的鉴别诊断提供实验依据。方法:采用组织芯片技术检测病理诊断明确的34例胃癌患者的胃癌组织标本及相对应的距胃癌组织边缘1.5cm处的组织、距胃癌组织边缘5cm以上的正常组织以及胃炎组织中HSP27的表达,RT-PCR法对8例患者的胃癌组织及其对应的正常胃黏膜组织、胃溃疡组织和慢性胃炎组织的HSP27 mRNA表达情况进行检测。比较组织芯片中胃癌与癌旁以及胃癌与正常胃黏膜组织之间HSP27蛋白的表达差异,并比较HSP27 mRNA的表达情况。结果:HSP27蛋白主要表达于细胞质中,少量表达于细胞核及细胞膜;HSP27蛋白在胃癌、癌旁、正常胃黏膜组织及胃炎中的表达阳性率分别为52.94%、11.78%、14.71%和5.88%,过表达率分别为38.24%、11.77%、11.77%和5.88%。HSP27蛋白在胃癌中的表达量明显高于胃癌旁组织、胃炎组织及正常胃黏膜组织(P<0.01)。在mRNA水平,胃癌组织的HSP27表达也明显高于其余3组(P<0.01)。结论:胃癌中HSP27的表达水平明显高于胃癌旁组织,胃炎组织和正常胃黏膜组织,HSP27有可能成为一种潜在性的用于鉴别良恶性胃黏膜病变的标志物。展开更多
文摘Cell protection from stresses by heat shock protein (HSP) was previously attributed to its ability to prevent aggregation and to accelerate refolding of damaged proteins. It plays an important role in cell survival after extremely harsh protein damaging treatment leading to necrotic cell death. On the other hand, protein repair function of HSP cannot explain how it protects cell from stresses which do not cause direct protein damage. These stresses kill cell through activation of apoptotic program. Recently it has been found that HSP can meditate suppression of a stress-activated protein kinase, JNK, an early component of stress-induced apoptotic signaling pathway.These observations can provide a basis for HSP’s function of anti-apoptosis.
基金supported by grants from the National Natural Science Foundation of China(31900146)the key Biosafety Science and Technology Program of Hubei Jiangxia Laboratory(JXBS001)+1 种基金the Hubei Natural Science Foundation for Distinguished Young Scholars(2021CFA050)the Creative Research Group Program of Natural Science Foundation of Hubei Province(2022CFA021).
文摘Severe fever with thrombocytopenia syndrome(SFTS)caused by the SFTS virus(SFTSV)is an emerging disease in East Asia with a fatality rate of up to 30%.However,the viral-host interaction of SFTSV remains largely unknown.The heat-shock protein 90(Hsp90)family consists of highly conserved chaperones that fold and remodel proteins and has a broad impact on the infection of many viruses.Here,we showed that Hsp90 is an important host factor involved in SFTSV infection.Hsp90 inhibitors significantly reduced SFTSV replication,viral protein expression,and the formation of inclusion bodies consisting of nonstructural proteins(NSs).Among viral proteins,NSs appeared to be the most reduced when Hsp90 inhibitors were used,and further analysis showed that their translation was affected.Co-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90βspecifically interacted with them.Knockdown of Hsp90βexpression also inhibited replication of SFTSV.These results suggest that Hsp90βplays a critical role during SFTSV infection and could be a potential target for the development of drugs against SFTS.
基金supported by the UK Medical Research Council(Grant No.MC_UU_12021/3 and MC_U137788471)University of OxfordShanghaiTech University
文摘The metabolic enzyme CTP synthase(CTPS) is able to compartmentalize into filaments,termed cytoophidia,in a variety of organisms including bacteria,budding yeast,fission yeast,fruit flies and mammals.A previous study in budding yeast shows that the filament-forming process of CTPS is not sensitive to temperature shift.Here we study CTPS filamentation in the fission yeast Schizosaccharomyces pombe.To our surprise,we find that both the length and the occurrence of cytoophidia in S.pombe decrease upon cold shock or heat shock.The temperature-dependent changes of cytoophidia are fast and reversible.Taking advantage of yeast genetics,we demonstrate that heat-shock proteins are required for cytoophidium assembly in S.pombe.Temperature sensitivity of cytoophidia makes S.pombe an attractive model system for future investigations of this novel membraneless organelle.
基金supported by the National Natural Science Foundation of China(21971153 ,21671122)the Major Basic Research Projects of Shandong Natural Science Foundation(ZR2020ZD32)+2 种基金the Taishan Scholars Climbing Program of Shandong Provincethe Natural Science Foundation of Shandong Province(ZR202102280580)China Postdoctoral Science Foundation(2020M682225)。
文摘Photothermal therapy(PTT)has shown promising applications in tumor therapies.However,due to laserinduced nonspecific heating and heat diffusion,high levels of hyperthermia(>50℃)in tumor tissues often increase the risk of cancer recurrence and metastasis,which causes the patient pain and destroys the surrounding normal cells and tissues.It is therefore important to develop photothermal strategies that have excellent therapeutic efficiencies under low-temperature conditions(≤45℃).In addition,the heterogeneity and complexity of tumors require the development of combinatorial antitumor treatments as the therapeutic efficiency of monomodal PTT is not currently sufficient.Herein,we have adopted a stepwise synthetic approach to develop a highly efficient multimodal therapeutic agent GA@PCOF@PDA by successive bonding defect functionalization(BDF),guest encapsulation,and surface modification steps.The covalently grafted porphyrinic photosensitizers(Por),encapsulated gambogic acid(GA),and surface-modified PDA film are independently responsible for photodynamic therapy(PDT),heat-shock protein 90(HSP90)down-regulation and chemotherapy(CT),and low-temperature PTT.This proof-ofconcept study illustrates an efficient,generalized approach to design high-performance covalent organic framework(COF)-based nanoagents that can be easily tailored to combine different therapeutic modalities for improved cancer theranostics at low temperatures.
基金supported by a grant from the Health Bureau of Henan Province,China(No.201003111)
文摘In the present study, we examined the effect of oxygen glucose deprivation（OGD） post-conditioning（PostC） on neural cell apoptosis in OGD-PostC model and the protective effect on primary cortical neurons against OGD injury in vitro. Four-h OGD was induced by OGD by using a specialized and humidified chamber. To initiate OGD, culture medium was replaced with de-oxygenated and glucose-free extracellular solution-Locke＇s medium. After OGD treatment for 4 h, cells were then allowed to recover for 6 h or 20 h. Then lactate dehydrogenase（LDH） release assay, Western blotting and flow cytometry were used to detect cell death, protein levels and apoptotic cells, respectively. For the PostC treatment, three cycles of 15-min OGD, followed by 15 min normal cultivation, were applied immediately after injurious 4-h OGD. Cells were then allowed to recover for 6 h or 20 h, and cell death was assessed by LDH release assay. Apoptotic cells were flow cytometrically evaluated after 4-h OGD, followed by re-oxygenation for 20 h（O4/R20）. In addition, Western blotting was used to examine the expression of heat-shock protein 70（HSP70）, Bcl-2 and Bax. The ratio of Bcl-2 expression was（0.44±0.08）% and（0.76±0.10）%, and that of Bax expression was（0.51±0.05）% and（0.39±0.04）%, and that of HSP70 was（0.42±0.031）% and（0.72±0.045）% respectively in OGD group and PostC group. After O4/R6, the rate of neuron death in PostC group and OGD groups was（28.96±3.03）% and（37.02±4.47）%, respectively. Therefore, the PostC treatment could up-regulate the expression of HSP70 and Bcl-2, but down-regulate Bax expression. As compared with OGD group, OGD-induced neuron death and apoptosis were significantly decreased in PostC group（P0.05）. These findings suggest that PostC inhibited OGD-induced neuron death. This neuro-protective effect is likely achieved by anti-apoptotic mechanisms and is associated with over-expression of HSP70.
