目的探讨乳腺癌中SIRT5的表达及其与PKM2及HK2相关性及临床意义。方法采用免疫组化SP法检测130例乳腺癌组织及癌旁正常组织中SIRT5、PKM2及HK2的表达,应用RT-PCR法检测60例乳腺癌组织及癌旁正常组织SIRT5、PKM2及HK2的基因表达,分析SIRT...目的探讨乳腺癌中SIRT5的表达及其与PKM2及HK2相关性及临床意义。方法采用免疫组化SP法检测130例乳腺癌组织及癌旁正常组织中SIRT5、PKM2及HK2的表达,应用RT-PCR法检测60例乳腺癌组织及癌旁正常组织SIRT5、PKM2及HK2的基因表达,分析SIRT5表达与乳腺癌临床病理特征的关系。结果乳腺癌组织中SIRT5、PKM2及HK2的平均光密度值均显著高于癌旁正常组织(5824.4±163.1 vs 2629.9±132.3、5980.3±232.2 vs 2164.9±121.3、6005.1±197.5 vs 2196.7±155.4,P<0.01),乳腺癌组织SIRT5、PKM2及HK2 mRNA的表达均高于癌旁正常组织(P<0.01)。乳腺癌组织中SIRT5与PKM2、HK2蛋白间呈正相关(r=0.647、r=0.600,P<0.01)。SIRT5阳性率与患者年龄、淋巴结转移、TNM分期、ER及PR表达差异无统计学意义(P=0.859,P=0.248,P=0.986,P=0.489,P=0.882);与肿瘤大小、组织学分级及HER-2表达差异有统计学意义(P=0.003,P=0.001,P=0.037)。结论SIRT5的过表达对判断乳腺癌的发生、发展及预后具有一定价值,并为SIRT5可能通过有氧糖酵解影响乳腺癌的发生、发展奠定基础。展开更多
目的:检测结肠癌中沉默调节蛋白5(Sirtuin 5,SIRT5)表达情况并探讨其与18氟-脱氧葡萄糖(;F-fluorodeoxyglucose,^(18)F-FDG)最大标准化摄取值(the maximum standardized uptake value,SUVmax)、葡萄糖转运蛋白1(glucose trans porter-1,...目的:检测结肠癌中沉默调节蛋白5(Sirtuin 5,SIRT5)表达情况并探讨其与18氟-脱氧葡萄糖(;F-fluorodeoxyglucose,^(18)F-FDG)最大标准化摄取值(the maximum standardized uptake value,SUVmax)、葡萄糖转运蛋白1(glucose trans porter-1,GLUT1)表达以及患者临床参数的关系。方法:回顾性分析78例术前行;F-FDG正电子发射型计算机断层扫描(positron emission tomography/computed tomography,PET/CT)的结直肠癌患者,免疫组化分析SIRT5、GLUT1蛋白表达,与SUVmax、临床参数、预后指标做相关分析。使用CRISPR/Cas9技术敲除SIRT5,研究其对结直肠癌细胞糖酵解以及缺氧诱导因子1α(hypoxia-inducible factor 1-alpha,HIF1α)转录活性的影响。结果:结直肠癌肿瘤组织中SIRT5较癌旁组织高表达(P <0.01),且高表达者预后欠佳(P <0.01)。结直肠癌低分化者SUVmax和SIRT5表达明显高于中高分化者(18.18±4.06 vs. 12.72±2.60,P <0.01;2.14±0.74 vs. 1.10±0.77,P <0.01)。结直肠癌患者SIRT5表达与SUVmax呈正相关(Spearman相关系数=0.648,P <0.05)。敲除SIRT5基因,抑制肿瘤细胞^(18)F-FDG摄取、GLUT1表达和HIF1α转录活性。结论:SIRT5可通过HIF1α/GLUT1促进结直肠癌^(18)F-FDG的摄取,SIRT5可能是结肠癌治疗的潜在靶点。展开更多
Progressive beta cell apoptosis is a major cause leading to a decline in beta cell mass in type 2 diabetes. While it has been discovered that mitochondrial protein Sirtuin 5 （ SIRT5 ） functions as the primary site o...Progressive beta cell apoptosis is a major cause leading to a decline in beta cell mass in type 2 diabetes. While it has been discovered that mitochondrial protein Sirtuin 5 （ SIRT5 ） functions as the primary site of oxidative metabolism and plays crucial roles in apoptosis and intracellular signaling, the contribution of SIRT5 in beta cell re- mains to be fully defined. Given the potential benefit of SIRT5 activation in cell metabolism, this study aimed to examine whether overexpression of SIRT5 in beta cells is sufficient to prevent saturated fatty acid induced impair- ment in insulin secretion and apoptosis, thus elucidating the role of SIRT5 in beta cell protection. In line with our previous study, two kinds of pancreatic beta cell lines were selected for the detection. Mouse-derived NIT-1 cells as well as human-derived PANC-1 cells were transfected with GFP-SIRT5-Ad plasmid and cell apoptosis was induced by palmitic acid （0.5 mM） , validated with TUNEL-DAPI double staining and RTCA iCelligence cell growth moni- tor system. Compared with control group, it was shown that SIRT5 overexpression could significantly reduce the quantity of apoptotic beta cells under chronic exposure to palmitic acid, accompanied with decreased Caspase 3 and Caspase 9 activities. Accordingly, cytochrome C oxidase activity in cells was also suppressed. Meanwhile, palmitic acid suppressed glucose-stimulated insulin secretion, but SIRT5 overexpression could recover the beta cell insulin secretion capacity against glucose fluctuation. Moreover, it is discovered that novel binding relationship exists be- tween SIRT5 and Bcl-XL, providing a reliable explanation for the anti-apoptosis role of SIRT5. Together, these re- sults reveal a potential role of SIRT5 in improvement of saturated fatty acid -induced beta cell dysfunction and apop- tosis. Considering the role of beta cell apoptosis in T2DM, overexpression or activation of SIRT5 may provide an e-rumpent approach as a potential target for beta cell protection. This approach might actually reverse the disease to a degree rather than just palliate glycemia.展开更多
文摘目的探讨乳腺癌中SIRT5的表达及其与PKM2及HK2相关性及临床意义。方法采用免疫组化SP法检测130例乳腺癌组织及癌旁正常组织中SIRT5、PKM2及HK2的表达,应用RT-PCR法检测60例乳腺癌组织及癌旁正常组织SIRT5、PKM2及HK2的基因表达,分析SIRT5表达与乳腺癌临床病理特征的关系。结果乳腺癌组织中SIRT5、PKM2及HK2的平均光密度值均显著高于癌旁正常组织(5824.4±163.1 vs 2629.9±132.3、5980.3±232.2 vs 2164.9±121.3、6005.1±197.5 vs 2196.7±155.4,P<0.01),乳腺癌组织SIRT5、PKM2及HK2 mRNA的表达均高于癌旁正常组织(P<0.01)。乳腺癌组织中SIRT5与PKM2、HK2蛋白间呈正相关(r=0.647、r=0.600,P<0.01)。SIRT5阳性率与患者年龄、淋巴结转移、TNM分期、ER及PR表达差异无统计学意义(P=0.859,P=0.248,P=0.986,P=0.489,P=0.882);与肿瘤大小、组织学分级及HER-2表达差异有统计学意义(P=0.003,P=0.001,P=0.037)。结论SIRT5的过表达对判断乳腺癌的发生、发展及预后具有一定价值,并为SIRT5可能通过有氧糖酵解影响乳腺癌的发生、发展奠定基础。
文摘Progressive beta cell apoptosis is a major cause leading to a decline in beta cell mass in type 2 diabetes. While it has been discovered that mitochondrial protein Sirtuin 5 （ SIRT5 ） functions as the primary site of oxidative metabolism and plays crucial roles in apoptosis and intracellular signaling, the contribution of SIRT5 in beta cell re- mains to be fully defined. Given the potential benefit of SIRT5 activation in cell metabolism, this study aimed to examine whether overexpression of SIRT5 in beta cells is sufficient to prevent saturated fatty acid induced impair- ment in insulin secretion and apoptosis, thus elucidating the role of SIRT5 in beta cell protection. In line with our previous study, two kinds of pancreatic beta cell lines were selected for the detection. Mouse-derived NIT-1 cells as well as human-derived PANC-1 cells were transfected with GFP-SIRT5-Ad plasmid and cell apoptosis was induced by palmitic acid （0.5 mM） , validated with TUNEL-DAPI double staining and RTCA iCelligence cell growth moni- tor system. Compared with control group, it was shown that SIRT5 overexpression could significantly reduce the quantity of apoptotic beta cells under chronic exposure to palmitic acid, accompanied with decreased Caspase 3 and Caspase 9 activities. Accordingly, cytochrome C oxidase activity in cells was also suppressed. Meanwhile, palmitic acid suppressed glucose-stimulated insulin secretion, but SIRT5 overexpression could recover the beta cell insulin secretion capacity against glucose fluctuation. Moreover, it is discovered that novel binding relationship exists be- tween SIRT5 and Bcl-XL, providing a reliable explanation for the anti-apoptosis role of SIRT5. Together, these re- sults reveal a potential role of SIRT5 in improvement of saturated fatty acid -induced beta cell dysfunction and apop- tosis. Considering the role of beta cell apoptosis in T2DM, overexpression or activation of SIRT5 may provide an e-rumpent approach as a potential target for beta cell protection. This approach might actually reverse the disease to a degree rather than just palliate glycemia.
