目的:探讨烟酰胺磷酸核糖转移酶(NAMPT)在多发性骨髓瘤中的作用机制及其临床价值。方法:采用RT-q PCR和Western blot方法检测多发性骨髓瘤细胞和正常骨髓单个核细胞中NAMPT的表达水平,同时通过细胞增殖与凋亡实验、小干扰RNA沉默、过表...目的:探讨烟酰胺磷酸核糖转移酶(NAMPT)在多发性骨髓瘤中的作用机制及其临床价值。方法:采用RT-q PCR和Western blot方法检测多发性骨髓瘤细胞和正常骨髓单个核细胞中NAMPT的表达水平,同时通过细胞增殖与凋亡实验、小干扰RNA沉默、过表达实验和染色质免疫共沉淀实验分析NAMPT的生物学功能。结果:多发性骨髓瘤细胞系(MM1R、MM1S、U266和RPMI-8226)中NAMPT m RNA和蛋白的表达水平较正常骨髓单个核细胞均显著升高(P<0.001),且在U266细胞中最明显。与Si-NC组相比,Si-NAMPT组转染24、48、72 h均显著抑制U266细胞增殖(P=0.006,P<0.001,P=0.001),转染48 h时U266细胞凋亡率升高显著(P<0.001)。与Flag-NC组比较,Flag-NAMPT组U266细胞增殖均显著升高(P=0.003,P=0.002,P<0.001),转染48 h时细胞凋亡率明显降低。在U266细胞中NAMPT的表达在转录水平受到XBP1的调控。用硼替佐米处理XBP1或NAMPT稳定敲除或经MKC3946预处理的U266细胞后细胞增殖率均显著下降,BAX m RNA和蛋白水平显著升高,BCL-2 m RNA和蛋白水平显著下调,Caspase-3裂解度显著下降,Caspase-3/7活性急剧增加(P<0.05)。结论:NAMPT在多发性骨髓瘤细胞系中高表达,促进多发性骨髓瘤细胞增殖,抑制细胞凋亡。在U266细胞中NAMPT受IRE1α-XBP1信号通路的转录调控。稳定敲除NAMPT或阻断IRE1α-XBP1通路可显著提高U266细胞对硼替佐米的敏感性。展开更多
目的探讨内脂素-烟酰胺磷酸核糖转移酶(Nampt)轴在卵巢上皮癌进展中的作用及对患者预后的影响。方法采用免疫组化方法检测Nampt在卵巢上皮癌及正常卵巢组织内的表达,ELISA方法测定血清内脂素浓度,并分析其与临床病理特征及患者总体生存...目的探讨内脂素-烟酰胺磷酸核糖转移酶(Nampt)轴在卵巢上皮癌进展中的作用及对患者预后的影响。方法采用免疫组化方法检测Nampt在卵巢上皮癌及正常卵巢组织内的表达,ELISA方法测定血清内脂素浓度,并分析其与临床病理特征及患者总体生存期的关系。结果卵巢上皮癌患者血清内脂素浓度显著高于卵巢良性肿瘤患者及正常对照人群,内脂素诊断卵巢上皮癌的曲线下面积(area under curve,AUC)为0.744,界值5.95 ng/mL。卵巢上皮癌患者血清内脂素与T、N、FIGO分期相关(P<0.05)且与CA125呈正相关性(rs=0.389,P=0.001)。Nampt在卵巢上皮癌组织中阳性表达率显著升高,且与FIGO分期、血清内脂素水平相关(P<0.05)。卵巢上皮肿瘤细胞Nampt蛋白表达与患者血清内脂素水平呈正相关性(rs=0.55,P<0.001)。卵巢上皮癌患者1年、3年、5年生存率分别为98.6%、74.3%、34.3%。生存分析显示,卵巢上皮癌患者生存期与T、N、FIGO分期及血清内脂素、肿瘤细胞Nampt表达有关,且FIGO分期、肿瘤细胞Nampt表达是影响患者预后的独立因素(P<0.05)。结论卵巢上皮癌患者血清内脂素、癌组织中Nampt高表达以及T、N、FIGO分期与患者总体生存期有关,且Nampt高表达、FIGO分期是独立影响因素。这提示内脂素-Nampt轴促进卵巢上皮癌进展并影响患者预后。展开更多
Aim Nicotinamide phosphoribosyltransferase （NAMPT）, also an adipokine known as visfatin, acts via enzymatic activity to synthesize nicotinamide mononucleotide （NMN） and then maintain homeostasis of nicotinam- ide ...Aim Nicotinamide phosphoribosyltransferase （NAMPT）, also an adipokine known as visfatin, acts via enzymatic activity to synthesize nicotinamide mononucleotide （NMN） and then maintain homeostasis of nicotinam- ide adenine dinucleotide （NAD）, which plays a dual role in energy metabolism and biological signaling. Of note, the NAMPT metabolic pathway connects NAD-dependent sirtuin signaling, constituting a strong intrinsic defense system against various stresses. Most recently, we and others have demonstrated several mechanisms by which NAMPT might serve as a therapeutic target against ischemic stroke, including cerebroprotection in the acute phase as well as vascular repair and neurogenesis in the chronic phase. The molecular mechanisms underlying these bene- fits have been explored in vivo and in vitro for neural cells, endothelial progenitor cells, and neural stem cells. Therapeutic interventions using NMN, NAMPT activators and ischemic conditioning are promising for stroke salvage and rehabilitation. Here, we discuss the current NAMPT data in the context of translational efforts for stroke treat- ment.展开更多
文摘目的:探讨烟酰胺磷酸核糖转移酶(NAMPT)在多发性骨髓瘤中的作用机制及其临床价值。方法:采用RT-q PCR和Western blot方法检测多发性骨髓瘤细胞和正常骨髓单个核细胞中NAMPT的表达水平,同时通过细胞增殖与凋亡实验、小干扰RNA沉默、过表达实验和染色质免疫共沉淀实验分析NAMPT的生物学功能。结果:多发性骨髓瘤细胞系(MM1R、MM1S、U266和RPMI-8226)中NAMPT m RNA和蛋白的表达水平较正常骨髓单个核细胞均显著升高(P<0.001),且在U266细胞中最明显。与Si-NC组相比,Si-NAMPT组转染24、48、72 h均显著抑制U266细胞增殖(P=0.006,P<0.001,P=0.001),转染48 h时U266细胞凋亡率升高显著(P<0.001)。与Flag-NC组比较,Flag-NAMPT组U266细胞增殖均显著升高(P=0.003,P=0.002,P<0.001),转染48 h时细胞凋亡率明显降低。在U266细胞中NAMPT的表达在转录水平受到XBP1的调控。用硼替佐米处理XBP1或NAMPT稳定敲除或经MKC3946预处理的U266细胞后细胞增殖率均显著下降,BAX m RNA和蛋白水平显著升高,BCL-2 m RNA和蛋白水平显著下调,Caspase-3裂解度显著下降,Caspase-3/7活性急剧增加(P<0.05)。结论:NAMPT在多发性骨髓瘤细胞系中高表达,促进多发性骨髓瘤细胞增殖,抑制细胞凋亡。在U266细胞中NAMPT受IRE1α-XBP1信号通路的转录调控。稳定敲除NAMPT或阻断IRE1α-XBP1通路可显著提高U266细胞对硼替佐米的敏感性。
文摘目的探讨内脂素-烟酰胺磷酸核糖转移酶(Nampt)轴在卵巢上皮癌进展中的作用及对患者预后的影响。方法采用免疫组化方法检测Nampt在卵巢上皮癌及正常卵巢组织内的表达,ELISA方法测定血清内脂素浓度,并分析其与临床病理特征及患者总体生存期的关系。结果卵巢上皮癌患者血清内脂素浓度显著高于卵巢良性肿瘤患者及正常对照人群,内脂素诊断卵巢上皮癌的曲线下面积(area under curve,AUC)为0.744,界值5.95 ng/mL。卵巢上皮癌患者血清内脂素与T、N、FIGO分期相关(P<0.05)且与CA125呈正相关性(rs=0.389,P=0.001)。Nampt在卵巢上皮癌组织中阳性表达率显著升高,且与FIGO分期、血清内脂素水平相关(P<0.05)。卵巢上皮肿瘤细胞Nampt蛋白表达与患者血清内脂素水平呈正相关性(rs=0.55,P<0.001)。卵巢上皮癌患者1年、3年、5年生存率分别为98.6%、74.3%、34.3%。生存分析显示,卵巢上皮癌患者生存期与T、N、FIGO分期及血清内脂素、肿瘤细胞Nampt表达有关,且FIGO分期、肿瘤细胞Nampt表达是影响患者预后的独立因素(P<0.05)。结论卵巢上皮癌患者血清内脂素、癌组织中Nampt高表达以及T、N、FIGO分期与患者总体生存期有关,且Nampt高表达、FIGO分期是独立影响因素。这提示内脂素-Nampt轴促进卵巢上皮癌进展并影响患者预后。
文摘Aim Nicotinamide phosphoribosyltransferase （NAMPT）, also an adipokine known as visfatin, acts via enzymatic activity to synthesize nicotinamide mononucleotide （NMN） and then maintain homeostasis of nicotinam- ide adenine dinucleotide （NAD）, which plays a dual role in energy metabolism and biological signaling. Of note, the NAMPT metabolic pathway connects NAD-dependent sirtuin signaling, constituting a strong intrinsic defense system against various stresses. Most recently, we and others have demonstrated several mechanisms by which NAMPT might serve as a therapeutic target against ischemic stroke, including cerebroprotection in the acute phase as well as vascular repair and neurogenesis in the chronic phase. The molecular mechanisms underlying these bene- fits have been explored in vivo and in vitro for neural cells, endothelial progenitor cells, and neural stem cells. Therapeutic interventions using NMN, NAMPT activators and ischemic conditioning are promising for stroke salvage and rehabilitation. Here, we discuss the current NAMPT data in the context of translational efforts for stroke treat- ment.
