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https://www.readbyqxmd.com/read/28715126/an-engineered-photoswitchable-mammalian-pyruvate-kinase
#1
Stefanie Gehrig, Jamie A Macpherson, Paul C Driscoll, Alastair Symon, Stephen R Martin, James I MacRae, Jens Kleinjung, Franca Fraternali, Dimitrios Anastasiou
Changes in allosteric regulation of glycolytic enzymes have been linked to metabolic reprogramming involved in cancer. Remarkably, allosteric mechanisms control enzyme function at significantly shorter time-scales compared to the long-term effects of metabolic reprogramming on cell proliferation. It remains unclear if and how the speed and reversibility afforded by rapid allosteric control of metabolic enzymes is important for cell proliferation. Tools that allow specific, dynamic modulation of enzymatic activities in mammalian cells would help address this question...
July 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28709426/xue-fu-zhu-yu-decoction-protects-rats-against-retinal-ischemia-by-downregulation-of-hif-1%C3%AE-and-vegf-via-inhibition-of-rbp2-and-pkm2
#2
Shu-Qiu Tan, Xue Geng, Jorn-Hon Liu, Wynn Hwai-Tzong Pan, Li-Xiang Wang, Hui-Kang Liu, Lei Hu, Hsiao-Ming Chao
BACKGROUND: Retinal ischemia-related eye diseases result in visual dysfunction. This study investigates the protective effects and mechanisms of Xue-Fu-Zhu-Yu decoction (XFZYD) with respect to retinal ischemia. METHODS: Retinal ischemia (I) was induced in Wistar rats by a high intraocular pressure (HIOP) of 120 mmHg for 1 h, which was followed by reperfusion of the ischemic eye; the fellow untreated eye acted as a control. Electroretinogram (ERG), biochemistry and histopathology investigations were performed...
July 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28689265/aerobic-glycolysis-hypothesis-through-wnt-beta-catenin-pathway-in-exudative-age-related-macular-degeneration
#3
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Exudative age-related macular degeneration (AMD) is characterized by molecular mechanisms responsible for the initiation of choroidal neovascularization (CNV). Inflammatory processes are associated with upregulation of the canonical WNT/beta-catenin pathway in exudative AMD. We focus this review on the link between WNT/beta-catenin pathway activation and neovascular progression in exudative AMD through activation of aerobic glycolysis for production of angiogenic factors. Increased WNT/beta-catenin pathway involves hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2)...
July 8, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28688274/discovery-of-novel-naphthoquinone-derivatives-as-inhibitors-of-the-tumor-cell-specific-m2-isoform-of-pyruvate-kinase
#4
Xianling Ning, Hailong Qi, Ridong Li, Yunqiao Li, Yan Jin, Michael A McNutt, Junyi Liu, Yuxin Yin
Pyruvate kinase M2 (PKM2) is a rate-limiting enzyme of the glycolytic pathway which is highly expressed in cancer cells. Cancer cells rely heavily on PKM2 for anabolic and energy requirements, and specific targeting of PKM2 therefore has potential as strategy for cancer therapy. Here, we report the synthesis and biologic evaluation of novel naphthoquinone derivatives as selective small molecule inhibitors of PKM2. Some target compounds, such as compound 3k, displayed more potent PKM2 inhibitory activity than the reported optimal PKM2 inhibitor shikonin...
June 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28641694/-mir-133b-affect-the-proliferation-and-drug-sensitivity-in-a549-lung-cancer-stem-cells-by-targeting-pkm2
#5
Yonghua Mi, Miao He, Beizhong Liu
BACKGROUND: It has been proven that miR-133b could inhibit cancer cell growth, the expression level of miR-133b was significant reduction in lung cancer tissue and serum of patients, and increase the radiation sensitivity of squamous cell carcinoma by targeting PKM2, but the exist mechanisms is not clear. The aim of this study is to explore the effect of miR-133b on proliferation in A549 lung cancer stem cells and drug sensitivity in DDP, and to explore the relationship between miR-133b and PKM2 gene, as well as the effect of cancer stem cells...
June 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28641457/antiglioma-pseurotin-a-from-marine-bacillus-sp-fs8d-regulating-tumour-metabolic-enzymes
#6
Komal Anjum, Hongyun Bi, Weiyun Chai, Xiao-Yuan Lian, Zhizhen Zhang
Pseurotin A was isolated from a culture of marine Bacillus sp. FS8D and showed to be active against the proliferation of four different glioma cells with IC50 values of 0.51-29.3 μM. It has been found that pseurotin A downregulated the expression of tumour glycolytic enzymes pyruvate kinase M2 (PKM2) and lactate dehydrogenase 5 (LDH5) and upregulated the expression of pyruvate dehydrogenase beta (PDHB), adenosine triphosphate synthase beta (ATPB) and cytochrome C (Cyto-C), the important regulators for tricarboxylic acid cycle and oxidative phosphorylation...
June 23, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28630053/glucose-catabolism-in-liver-tumors-induced-by-c-myc-can-be-sustained-by-various-pkm1-pkm2-ratios-and-pyruvate-kinase-activities
#7
Andrés Méndez-Lucas, Xiaolei Li, Junjie Hu, Li Che, Xinhua Song, Jiaoyuan Jia, Jingxiao Wang, Chencheng Xie, Paul C Driscoll, Darjus F Tschaharganeh, Diego F Calvisi, Mariia Yuneva, Xin Chen
Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Due to differential regulation of enzymatic activities, PKM2 but not PKM1 has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL...
June 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28627476/deciphering-the-protein-protein-interaction-network-regulating-hepatocellular-carcinoma-metastasis
#8
Guoxuan Qin, Mengjiao Dang, Huajun Gao, Hao Wang, Fengting Luo, Ruibing Chen
Hepatocellular carcinoma (HCC) is one of the leading causes of mortality related to cancer all over the world. To better understand the molecular mechanisms of HCC metastasis, we analyzed the proteome of three HCC cell lines with different metastasis potentials by quantitative proteomics and bioinformatics analysis. As a result, we identified 378 cellular proteins potentially associated to HCC metastasis, and constructed a highly connected protein-protein interaction (PPI) network. Functional annotation of the network uncovered prominent pathways and key roles of these proteins, suggesting that the metabolism and cytoskeleton biological processes are greatly involved with HCC metastasis...
June 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28626035/cyclin-d3-cdk6-has-a-metabolic-prosurvival-role-in-t-all
#9
(no author information available yet)
Cyclin D3-CDK6 inhibits the glycolytic enzymes PFK1 and PKM2 to prevent T-ALL cell apoptosis.
June 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28614718/sirt5-desuccinylates-and-activates-pyruvate-kinase-m2-to-block-macrophage-il-1%C3%AE-production-and-to-prevent-dss-induced-colitis-in-mice
#10
Fang Wang, Ke Wang, Wei Xu, Shimin Zhao, Dan Ye, Yi Wang, Ying Xu, Lisha Zhou, Yiwei Chu, Cuiping Zhang, Xue Qin, Pengyuan Yang, Hongxiu Yu
LPS-activated macrophages undergo a metabolic shift from dependence on mitochondria-produced ATP to reliance on aerobic glycolysis, where PKM2 is a critical determinant. Here, we show that PKM2 is a physiological substrate of SIRT5 and that SIRT5-regulated hypersuccinylation inhibits the pyruvate kinase activity of PKM2 by promoting its tetramer-to-dimer transition. Moreover, a succinylation-mimetic PKM2 K311E mutation promotes nuclear accumulation and increases protein kinase activity. Furthermore, we show that SIRT5-dependent succinylation promotes PKM2 entry into nucleus, where a complex of PKM2-HIF1α is formed at the promoter of IL-1β gene in LPS-stimulated macrophages...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28588255/pkm2-promotes-cell-migration-and-inhibits-autophagy-by-mediating-pi3k-akt-activation-and-contributes-to-the-malignant-development-of-gastric-cancer
#11
Chao Wang, Jinling Jiang, Jun Ji, Qu Cai, Xuehua Chen, Yingyan Yu, Zhenggang Zhu, Jun Zhang
Pyruvate kinase M2 (PKM2) is a key kinase of glycolysis and is characteristic of all proliferating cells. The role of PKM2 in gastric cancer (GC) is still ambiguous and yet to be determined. To better understand the role of PKM2 in both the migration and invasion of GC, we measured the expression of PKM2 in GC cell lines using qRT-PCR and western blot. The prognostic value of PKM2 was analyzed by Immunohistochemistry in a cohort containing 88 GC patients. PKM2 was knocked down by the short hairpin RNA plasmid vector in NCI-N87 and BGC-823 cells, and the biological behavior and downstream signaling pathways were also investigated in vitro...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28583828/pkm2-mediated-inhibition-of-autophagy-facilitates-tat-s-inducing-hiv-1-transactivation
#12
Hong-Sheng Zhang, Zhong-Guo Zhang, Zhen Zhou, Guang-Yuan Du, Hu Li, Xiao-Ying Yu, Ying-Hui Huang
Considerable evidence has shown that autophagy has an important role in HIV-1 infection. However, it is still unknown whether metabolism-regulated autophagy pathway is involved in Tat-mediated HIV-1 transactivation. This study demonstrated that treatment of Tat in TZM-bl cells significantly down-regulated protein levels of Beclin-1, Atg-5, Atg-7, and LC3B-II and up-regulated of p62 levels. Blockage of autophagy enhanced Tat-induced HIV-1 transactivation in TZM-bl cells. Moreover, we found that Tat activated the Akt/mTOR and inhibited AMPK signaling pathway that was related to its up-regulation of PKM2 expression...
June 2, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28577299/upa-upar-system-activation-drives-a-glycolytic-phenotype-in-melanoma-cells
#13
Anna Laurenzana, Anastasia Chillà, Cristina Luciani, Silvia Peppicelli, Alessio Biagioni, Francesca Bianchini, Elena Tenedini, Eugenio Torre, Alessandra Mocali, Lido Calorini, Francesca Margheri, Gabriella Fibbi, Mario Del Rosso
In this manuscript, we show the involvement of the uPA/uPAR system in the regulation of aerobic glycolysis of melanoma cells. uPAR over-expression in human melanoma cells controls an invasive and glycolytic phenotype in normoxic conditions. uPAR down-regulation by siRNA or its uncoupling from integrins, and hence from integrin-linked tyrosine kinase receptors (IL-TKRs), by an antagonist peptide induced a striking inhibition of the PI3K/AKT/mTOR/HIF1α pathway, resulting into impairment of glucose uptake, decrease of several glycolytic enzymes and of PKM2, a checkpoint that controls metabolism of cancer cells...
June 2, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28573168/analysis-of-in-vivo-interaction-between-rna-binding-proteins-and-their-rna-targets-by-uv-cross-linking-and-immunoprecipitation-clip-method
#14
Pamela Bielli, Claudio Sette
RNA metabolism is tightly controlled across different tissues and developmental stages, and its dysregulation is one of the molecular hallmarks of cancer. Through direct binding to specific sequence element(s), RNA binding proteins (RBPs) play a pivotal role in co- and post-transcriptional RNA regulatory events. We have recently demonstrated that, in pancreatic cancer cells, acquisition of a drug resistant (DR)-phenotype relied on upregulation of the polypyrimidine tract binding protein (PTBP1), which in turn is recruited to the pyruvate kinase pre-mRNA and favors splicing of the oncogenic PKM2 variant...
May 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28569774/rgd-modified-oncolytic-adenovirus-harboring-shpkm2-exhibits-a-potent-cytotoxic-effect-in-pancreatic-cancer-via-autophagy-inhibition-and-apoptosis-promotion
#15
Yanni Xu, Liang Chu, Sujing Yuan, Yuanqin Yang, Yu Yang, Bin Xu, Kangjian Zhang, Xin-Yuan Liu, Ruwei Wang, Ling Fang, Zhinan Chen, Zongsuo Liang
The M2 isoform of pyruvate kinase (PKM2) is a key driver of glycolysis in cancer cells and has critical 'non-metabolic' functions in some cancers; however, the role of PKM2 in pancreatic cancer remains unclear. The aim of the current study was to elucidate the role of PKM2 in pancreatic cancer progression and the potential of PKM2 as a therapeutic target. In this study, we observed that PKM2 is highly expressed in patients with pancreatic cancer and is correlated to survival. Elevated PKM2 expression promoted cell proliferation, migration and tumor formation...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28569381/lncrna-tp53tg1-participated-in-the-stress-response-under-glucose-deprivation-in-glioma
#16
Xin Chen, Yang Gao, Deheng Li, Bin Hao, Yiqun Cao
Gliomas are the most common brain tumors of the center nervous system. And long non-coding RNAs (lncRNAs) are non-protein coding transcripts, which have been considered as one type of gene expression regulator for cancer development. In this study, we investigated the role of lncRNA-TP53TG1 in response to glucose deprivation in human gliomas. The expression levels of TP53TG1 in glioma tissues and cells were analyzed by qRT-PCR. In addition, the influence of TP53TG1 on glucose metabolism related genes at the mRNA level during both high and low glucose treatment was detected by qRT-PCR...
June 1, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543190/effects-of-shrna-mediated-silencing-of-pkm2-gene-on-aerobic-glycolysis-cell-migration-cell-invasion-and-apoptosis-in-colorectal-cancer-cells
#17
Xiao-Ling Yan, Xue-Bin Zhang, Ran Ao, Lin Guan
This study aims to explore the effects of shRNA-mediated silencing on Pyruvate kinase type M2 (PKM2) gene during aerobic glycolysis in colorectal cancer (CRC) cells. CRC tissues and adjacent normal tissues were obtained from 136 patients diagnosed with qRT-PCR, Western blotting and immunohistochemistry (IHC) were performed to detect mRNA and protein expressions of PKM2. CRC cells were divided into a blank, vector and PKM2-shRNA groups. Hexokinase (HK) and PKM2 activity were both determined by glucose-6-phosphate dehydrogenase (G-6-PD) coupled colorimetric assay and enzyme coupling rate method...
May 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28522551/inhibition-of-mir-143-during-ischemia-cerebral-injury-protects-neurons-through-recovery-of-the-hexokinase-2-mediated-glucose%C3%A2-uptake
#18
Xianzhu Zeng, Na Liu, Jing Zhang, Lei Wang, Zhecheng Zhang, Ju Zhu, Qian Li, Yuwen Wang
Ischemic stroke, a major cause of death, is caused by occlusion of a blood vessel, resulting in a significant reduction in regional cerebral blood flow. MicroRNAs (miRNAs) are a family of short noncoding RNAs (18 to 22 nucleotides) and bind the 3' un-translated region (UTR) of their target genes to post-transcriptionally suppress gene expression. In this study, we report miR-143 is downregulated in rat neurons but high expressed in astrocytes cells. In vivo middle cerebral artery occlusion (MCAO) and ex vivo oxygen-glucose deprivation (OGD) results showed miR-143 was significantly induced by ischemia injury...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28515149/pyruvate-kinase-inhibits-proliferation-during-postnatal-cerebellar-neurogenesis-and-suppresses-medulloblastoma-formation
#19
Katherine Tech, Andrey P Tikunov, Hamza Farooq, A Sorana Morrissy, Jessica Meidinger, Taylor Fish, Sarah C Green, Hedi Liu, Yisu Li, Andrew J Mungall, Richard A Moore, Yussanne Ma, Steven J M Jones, Marco A Marra, Matthew G Vander Heiden, Michael D Taylor, Jeffrey M Macdonald, Timothy R Gershon
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron progenitors (CGNP) and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting pyruvate kinase-M (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation, and tumorigenesis...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28511909/discovery-and-structure-guided-fragment-linking-of-4-2-3-dichlorobenzoyl-1-methyl-pyrrole-2-carboxamide-as-a-pyruvate-kinase-m2-activator
#20
Yumi Matsui, Isao Yasumatsu, Takashi Asahi, Takahiro Kitamura, Kazuo Kanai, Osamu Ubukata, Hitoshi Hayasaka, Sachiko Takaishi, Hiroyuki Hanzawa, Shinichi Katakura
Tumor cells switch glucose metabolism to aerobic glycolysis by expressing the pyruvate kinase M2 isoform (PKM2) in a low active form, providing glycolytic intermediates as building blocks for biosynthetic processes, and thereby supporting cell proliferation. Activation of PKM2 should invert aerobic glycolysis to an oxidative metabolism and prevent cancer growth. Thus, PKM2 has gained attention as a promising cancer therapy target. To obtain novel PKM2 activators, we conducted a high-throughput screening (HTS)...
July 1, 2017: Bioorganic & Medicinal Chemistry
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