BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic signific...BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.展开更多
AIM: To address the effect of heat-shock protein 90(HSP90) inhibitors on the release of the hepatitis C virus(HCV), a cell culture-derived HCV(JFH1/HCVcc) from Huh-7 cells was examined.METHODS: We quantified both the ...AIM: To address the effect of heat-shock protein 90(HSP90) inhibitors on the release of the hepatitis C virus(HCV), a cell culture-derived HCV(JFH1/HCVcc) from Huh-7 cells was examined.METHODS: We quantified both the intracellular and extracellular(culture medium) levels of the components(RNA and core) of JFH-1/HCVcc. The intracellular HCV RNA and core levels were determined after the JFH1/HCVcc-infected Huh-7 cells were treated with radicicol for 36 h. The extracellular HCV RNA and core protein levels were determined from the medium of the last 24 h of radicicol treatment. To determine the possible role of the HSP90 inhibitor in HCV release, we examined the effect of a combined application of low doses of the HSP90 inhibitor radicicol and the RNA replication inhibitors cyclosporin A(Cs A) or interferon. Finally, we statistically examined the combined effect of radicicoland Cs A using the combination index(CI) and graphical representation proposed by Chou and Talalay.RESULTS: We found that the HSP90 inhibitors had greater inhibitory effects on the HCV RNA and core protein levels measured in the medium than inside the cells. This inhibitory effect was observed in the presence of a low level of a known RNA replication inhibitor(Cs A or interferon-α). Treating the cells with a combination of radicicol and cyclosporin A for 24 h resulted in significant synergy(CI < 1) that affected the release of both the viral RNA and the core protein. CONCLUSION: In addition to having an inhibitory effect on RNA replication, HSP90 inhibitors may interfere with an HCV replication step that occurs after the synthesis of viral RNA, such as assembly and release.展开更多
Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC3m cel...Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC3m cells were treated with 0-16μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10μmol/L antisense HSP70 oligomer for 48 hr or 8μtmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10μtmol/L antisense HSP70 oligomer treatment for 48 hr or 8μtmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abro-gates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression,in turn inducing apoptosis and inhibiting cell growth in PC-3m cells. (Asian JAndro12004 Dec;6:319-324)展开更多
Aim:To study the protein changes of spermatozoa associated with sperm motility during sperm cryopreservation and its mechanism.Methods:In 18 healthy men,the seminal sperm motility and HSP90 levels were studied before ...Aim:To study the protein changes of spermatozoa associated with sperm motility during sperm cryopreservation and its mechanism.Methods:In 18 healthy men,the seminal sperm motility and HSP90 levels were studied before and after cryopreservation using SDS-PAGE,Western blotting and computerized image analysis.Results:The sperm motility declined significantly after cryopreservation(P<0.01).The average grey level and the integrated grey level of sperm HSP90 before cooling were 34.1±3.2 and 243.0±21.6,respectively,while those after thawing were 23.2±2.5 and 105.7±28.5,respectively.Both parameters were decreased significantly(P<0.01).No HSP90 was found in the seminal plasma before and after cryopreservation.Conclusion:HSP90 in human spermatozoa was decreased substantially after cryopreservation.This may results from protein degradation,rather than leakage into the seminal plasma.展开更多
Pathological changes in the colon are closely associated with the spinal cord,and innervation of spinal cord can regulate cellular functions.Our previous studies verified that moxibustion protects and restores the col...Pathological changes in the colon are closely associated with the spinal cord,and innervation of spinal cord can regulate cellular functions.Our previous studies verified that moxibustion protects and restores the colonic mucosa,but the mechanisms of action remain unknown.The present study observed the effects of moxibustion and salicylazosulfapyridine on expression of heat-shock protein 70(HSP70) and its mRNA in the spinal cord and colonic mucosa of ulcerative colitis rats.Results demonstrated that moxibustion and salicylazosulfapyridine increased HSP70 mRNA expression in the spinal cord and colonic mucosa of ulcerative colitis rats.The decreased transcriptional activity of HSP70 in the spinal cord and colonic mucosa might participate in damage to the colonic mucosa in ulcerative colitis rats.Moxibustion exerted protective effects on colonic mucosa by up-regulating HSP70 transcriptional activity in the spinal cord and colonic mucosa.展开更多
The physiological mechanism of maintaining the green colour of pak choy leaves (Brassicarapa var chinensis) with heat-shock treatment was studied. Chlorophyll in the outerleaves of pak choy degraded rapidly during sto...The physiological mechanism of maintaining the green colour of pak choy leaves (Brassicarapa var chinensis) with heat-shock treatment was studied. Chlorophyll in the outerleaves of pak choy degraded rapidly during storage at ambient temperature (20±2℃), aslight yellow appeared. Heat-shock treatment (46-50℃) had a mild effect on maintainingthe green colour of outer leaves. Normal chlorophyll degradation was associated with abinding of chlorophyll with chlorophyll-binding-protein preceding chlorophyll breakdown.Heat-shock treatment was found to reduce the binding-capacity between chlorophyll-binding-protein and chlorophyll. In the chlorophyll degradation pathway, pheide dioxygenasewas synthesized during leaf senescence which was considered to be a key enzyme inchlorophyll degradation. Activity of this enzyme was reduced following heat-shocktreatment, which might explain the observed reduction in chlorophyll breakdown. Twogroups of heat-shock proteins were detected in treated leaves, the first group containingproteins from 54KDa to 74Kda, and the second group contained proteins from 15KDa to29KDa. Heat-shock treatment was also found to retard the decline of glucose and fructose(the main energy substrates) of outer leaves.展开更多
通过构建牛热休克蛋白A6(heat shock protein A6,HSPA6)序列与其他生物的系统进化树,以及运用生物信息学方法分析牛HSPA6蛋白的基本理化性质、亲疏水性等,并结合蛋白互作网络,探究牛HSPA6基因编码蛋白的结构和功能特性。结果显示,牛HSPA...通过构建牛热休克蛋白A6(heat shock protein A6,HSPA6)序列与其他生物的系统进化树,以及运用生物信息学方法分析牛HSPA6蛋白的基本理化性质、亲疏水性等,并结合蛋白互作网络,探究牛HSPA6基因编码蛋白的结构和功能特性。结果显示,牛HSPA6蛋白与羊、长江江豚等哺乳动物的氨基酸序列相似性较高;牛HSPA6蛋白分子质量为70 570.64 u,理论等电点为5.66,为酸性亲水性蛋白,无跨膜结构和信号肽;可能存在11个得分>0.900的磷酸化位点,与N-糖基化激活位点可能位于后端碱基;牛HSPA6蛋白是一种主要由40.38%的α-螺旋和33.65%的无规卷曲组成的二级结构相对稳定的蛋白质,包含N-端核苷酸结合域和C-端多肽结合域两个主要的结构域,主要在细胞质中发挥作用;蛋白质互作网络构建结果显示,牛HSPA6蛋白主要与BAG1、DNAJA4、DNAJB1、DNAJC2等蛋白发生互作,参与腺苷酸交换因子活性、ATP酶调节活性、伴侣绑定等,表明牛HSPA6蛋白在牛机体能量代谢等过程中发挥潜在生物学功能。这些多重生物信息学分析为深入探讨牛HSPA6蛋白对肉品质的影响机制提供了理论依据。展开更多
文摘BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.
文摘AIM: To address the effect of heat-shock protein 90(HSP90) inhibitors on the release of the hepatitis C virus(HCV), a cell culture-derived HCV(JFH1/HCVcc) from Huh-7 cells was examined.METHODS: We quantified both the intracellular and extracellular(culture medium) levels of the components(RNA and core) of JFH-1/HCVcc. The intracellular HCV RNA and core levels were determined after the JFH1/HCVcc-infected Huh-7 cells were treated with radicicol for 36 h. The extracellular HCV RNA and core protein levels were determined from the medium of the last 24 h of radicicol treatment. To determine the possible role of the HSP90 inhibitor in HCV release, we examined the effect of a combined application of low doses of the HSP90 inhibitor radicicol and the RNA replication inhibitors cyclosporin A(Cs A) or interferon. Finally, we statistically examined the combined effect of radicicoland Cs A using the combination index(CI) and graphical representation proposed by Chou and Talalay.RESULTS: We found that the HSP90 inhibitors had greater inhibitory effects on the HCV RNA and core protein levels measured in the medium than inside the cells. This inhibitory effect was observed in the presence of a low level of a known RNA replication inhibitor(Cs A or interferon-α). Treating the cells with a combination of radicicol and cyclosporin A for 24 h resulted in significant synergy(CI < 1) that affected the release of both the viral RNA and the core protein. CONCLUSION: In addition to having an inhibitory effect on RNA replication, HSP90 inhibitors may interfere with an HCV replication step that occurs after the synthesis of viral RNA, such as assembly and release.
文摘Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC3m cells were treated with 0-16μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10μmol/L antisense HSP70 oligomer for 48 hr or 8μtmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10μtmol/L antisense HSP70 oligomer treatment for 48 hr or 8μtmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abro-gates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression,in turn inducing apoptosis and inhibiting cell growth in PC-3m cells. (Asian JAndro12004 Dec;6:319-324)
文摘Aim:To study the protein changes of spermatozoa associated with sperm motility during sperm cryopreservation and its mechanism.Methods:In 18 healthy men,the seminal sperm motility and HSP90 levels were studied before and after cryopreservation using SDS-PAGE,Western blotting and computerized image analysis.Results:The sperm motility declined significantly after cryopreservation(P<0.01).The average grey level and the integrated grey level of sperm HSP90 before cooling were 34.1±3.2 and 243.0±21.6,respectively,while those after thawing were 23.2±2.5 and 105.7±28.5,respectively.Both parameters were decreased significantly(P<0.01).No HSP90 was found in the seminal plasma before and after cryopreservation.Conclusion:HSP90 in human spermatozoa was decreased substantially after cryopreservation.This may results from protein degradation,rather than leakage into the seminal plasma.
基金This work was supported by the National Natural Science Foundation of China （No. 30270796） Natural Science Foundation of Hebei Province, China （No. C2005000171）.
基金the National Basic Research Program of China (973 Program),No.2009CB522900the Shanghai Leading Academic Discipline Project,No.S30304
文摘Pathological changes in the colon are closely associated with the spinal cord,and innervation of spinal cord can regulate cellular functions.Our previous studies verified that moxibustion protects and restores the colonic mucosa,but the mechanisms of action remain unknown.The present study observed the effects of moxibustion and salicylazosulfapyridine on expression of heat-shock protein 70(HSP70) and its mRNA in the spinal cord and colonic mucosa of ulcerative colitis rats.Results demonstrated that moxibustion and salicylazosulfapyridine increased HSP70 mRNA expression in the spinal cord and colonic mucosa of ulcerative colitis rats.The decreased transcriptional activity of HSP70 in the spinal cord and colonic mucosa might participate in damage to the colonic mucosa in ulcerative colitis rats.Moxibustion exerted protective effects on colonic mucosa by up-regulating HSP70 transcriptional activity in the spinal cord and colonic mucosa.
文摘The physiological mechanism of maintaining the green colour of pak choy leaves (Brassicarapa var chinensis) with heat-shock treatment was studied. Chlorophyll in the outerleaves of pak choy degraded rapidly during storage at ambient temperature (20±2℃), aslight yellow appeared. Heat-shock treatment (46-50℃) had a mild effect on maintainingthe green colour of outer leaves. Normal chlorophyll degradation was associated with abinding of chlorophyll with chlorophyll-binding-protein preceding chlorophyll breakdown.Heat-shock treatment was found to reduce the binding-capacity between chlorophyll-binding-protein and chlorophyll. In the chlorophyll degradation pathway, pheide dioxygenasewas synthesized during leaf senescence which was considered to be a key enzyme inchlorophyll degradation. Activity of this enzyme was reduced following heat-shocktreatment, which might explain the observed reduction in chlorophyll breakdown. Twogroups of heat-shock proteins were detected in treated leaves, the first group containingproteins from 54KDa to 74Kda, and the second group contained proteins from 15KDa to29KDa. Heat-shock treatment was also found to retard the decline of glucose and fructose(the main energy substrates) of outer leaves.
