Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis

Background:The expression of pyruvate kinase muscle 2(PKM2)is augmented in macrophages of patients with atherosclerotic coronary artery disease.The role of PKM2 in atherosclerosis is to be determined.Methods:Global and myeloid cell-specific PKM2 knock-in mice with ApoE^(-/-)background(ApoE^(-/-),PKM2^(KI/KI)and Lyz2-cre,ApoE^(-/-),and PKM2^(flox/flox))were produced to evaluate the clinical significance of PKM2 in atherosclerosis development.Wild-type and PKM2 knock-in macrophages were isolated to assess the function of PKM2 in macrophage phagocytosis.Atherosclerotic mice were treated with PKM2 inhibitor shikonin(SKN)to evaluate the therapeutic potential of PKM2 suppression in atherosclerosis.Results:Oxidized low-density lipoprotein(oxLDL)upregulated PKM2 in macrophages.PKM2 in return promoted the uptake of oxLDL by macrophages.Overexpressed PKM2 accelerated atherosclerosis in mice.SKN blocked the progress of mouse atherosclerosis.Conclusions:PKM2 accelerates macrophage phagocytosis and atherosclerosis.Targeting PKM2 is a potential therapy for atherosclerosis.

Tumor pyruvate kinase M2:A promising molecular target of gastrointestinal cancer

Gastrointestinal(GI) cancer is one of the most common causes of cancer-related deaths worldwide.Tumor markers are valuable in detecting post-surgical recurrence or in monitoring response to chemotherapy.Pyruvate kinase isoform M2(PKM2),a glycolytic enzyme catalyzing conversion of phosphoenolpyruvate(PEP) to pyruvate,confers a growth advantage to the tumor cells and enables them to adapt to the tumor microenvironment.In this review,we have summarized current research on the expression and regulation of PKM2 in tumor cells,and its potential role in GI carcinogenesis and progression.Furthermore,we have also discussed the potential of PKM2 as a diagnostic and screening marker,and a therapeutic target in GI cancer.

SGOL1通过调节PKM2促进肺癌细胞增殖和侵袭

Shugoshin-1(SGOL1)是酵母Shugoshin的人类同源物之一,位于着丝粒区域,能够通过阻止着丝粒内聚复合物早熟分裂维持染色体稳定。近年来,SGOL1在肿瘤中的作用受到关注,但它在肺癌中的功能尚不清楚。本研究基于TCGA数据库分析发现,SGOL1在肺癌组织中高表达(n=529,P<0.00001),并与患者的不良预后呈正相关(P=0.0049)。qRT-PCR和Western印迹结果证实:SGOL1在肺癌细胞系表达水平均较正常肺上皮细胞的升高。在肺癌A549和NCI-H2405细胞系中,敲低SGOL1表达水平后,Cell Counting Kit-8(CCK8)实验、平板克隆实验、划痕愈合实验、Transwell实验结果分别提示,细胞的增殖、克隆形成、迁移、侵袭能力下降(P<0.05)。同时本研究发现,在TCGA数据中,丙酮酸激酶肌肉同工酶2(PKM2)和SGOL1的表达呈正相关性(r=0.38,P=0)。Western印迹检测显示,在肺癌细胞A549和NCI-H2405中,敲低SGOL1能下调PKM2的表达水平。此外,功能回补实验证实,过表达PKM2能部分逆转敲低SGOL1对肺癌细胞的增殖、克隆形成、迁移和侵袭能力的抑制作用。因此,本研究表明,SGOL1可能通过调节PKM2促进肺癌细胞的增殖和侵袭。本研究为SGOL1在肺癌中的作用机制提供理论依据。

丙酮酸激酶肌异构体2调控免疫细胞代谢的研究进展

丙酮酸激酶肌异构体2(pyruvate kinase muscle isoform 2,PKM2)是糖酵解的关键限速酶,也是免疫细胞代谢的重要调节因子。PKM2已被证明在多种炎症性疾病中过表达,并促进免疫细胞和炎症细胞的代谢和生物大分子的合成。PKM2的表达转变且激发了科研工作者对PKM2在免疫细胞中的作用机制和在炎症性疾病中治疗潜力的研究方向。此外,PKM2的结构和功能受一些激活剂和抑制剂的影响,研究人员揭示了PKM2的小分子激活剂和抑制剂的具体作用机制。免疫代谢重编程在炎症的发生、发展中起着至关重要的作用,因此,有必要明确PKM2在免疫代谢重编程中的作用。现就PKM2在不同免疫细胞中的作用,以及PKM2在免疫代谢重编程中的分子机制作一综述,期望有助于研究人员更好地了解PKM2的分子机制,从而帮助临床医生制定治疗策略。

清燥救肺汤对荷Lewis小鼠肺癌细胞糖酵解关键限速酶HK2,PFK2,PKM2的影响

目的:观察清燥救肺汤对荷Lewis小鼠肺癌细胞糖酵解关键限速酶己糖激酶2(hexokinase 2,HK2),6-磷酸果糖激酶2(phosphofructokinase,PFK2),M2型丙酮酸激酶(pyruvate kinase isoform M2,PKM2)的表达及葡萄糖含量的影响。方法:雄性C57BL/6J小鼠50只,随机分为模型组,环磷酰胺(cyclophosphamide,CTX)组,清燥救肺汤高、中、低剂量组,每组10只。所有小鼠右腋下注射Lewis肺癌细胞建立肺癌荷瘤模型,清燥救肺汤高、中、低剂量组剂量分别为11,5.5,2.75 g·kg^-1·d^-1,造模前2周开始灌胃给药,CTX组以50 mg·kg^-1·(2 d)-1腹腔注射给药,模型组以等体积生理盐水灌胃给药,接种后继续给药2周,处死小鼠取瘤组织;氧化酶法检测葡萄糖含量;实时荧光定量聚合酶链式反应(Real-time PCR)检测HK2 mRNA表达;蛋白质免疫印迹法(Western blot)检测PFK2蛋白表达;酶联免疫吸附测定(enzyme-linked immunesorbent assay,ELISA)检测PKM2活性。结果:与模型组比较,清燥救肺汤高、中、低剂量组肺癌细胞HK2 mRNA表达及PKM2活性显著降低,葡萄糖含量显著升高(P<0.01);与模型组比较,清燥救肺汤高、中剂量组肺癌细胞PFK2蛋白表达明显降低(P<0.05,P<0.01)。结论:清燥救肺汤可有效抑制荷Lewis肺癌细胞增殖,降低肺癌细胞葡萄糖摄取速率,糖酵解关键限速酶HK2,PFK2,PKM2可能是其药效作用靶点。