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https://www.readbyqxmd.com/read/27903739/homocysteine-activates-b-cells-via-regulating-pkm2-dependent-metabolic-reprogramming
#1
Jiacheng Deng, Silin Lü, Huiying Liu, Bo Liu, Changtao Jiang, Qingbo Xu, Juan Feng, Xian Wang
The overactivation of immune cells plays an important role in the pathogenesis of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis. Homocysteine (Hcy) activates B cell proliferation and Ab secretion; however, the underlying mechanisms for these effects remain largely unknown. Metabolic reprogramming is critical for lymphocyte activation and effector function. In this study, we showed that Hcy-activated B cells displayed an increase in both oxidative phosphorylation and glycolysis, with a tendency to shift toward the latter, as well as an accumulation of intermediates in the pentose phosphate pathway, to provide energy and biosynthetic substrates for cell growth and function...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27894667/nuclear-pkm2-expression-an-independent-risk-factor-for-er-after-curative-resection-of-hepatocellular-carcinoma
#2
Fangtian Fan, Hongyan Wu, Zhaoguo Liu, Xianbang Hou, Wenxin Chen, Aiyun Wang, Yin Lu
Surgical resection, providing a long-term survival of hepatocellular carcinoma (HCC) patients, is regarded as one of the standard curative treatments of HCC if the tumor is resectable. However, 50% patients develop early recurrence (ER) during the first two years after operation, which are more diffuse and rarely treatable with unsatisfactory long-term survival. Unfortunately, the underlying mechanisms of ER after curative resection and the molecular markers with predictive and prognostic significance have never been identified yet...
November 25, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27883057/the-warburg-effect-mediator-pyruvate-kinase-m2-expression-and-regulation-in-the-retina
#3
Raju V S Rajala, Ammaji Rajala, Christopher Kooker, Yuhong Wang, Robert E Anderson
The tumor form of pyruvate kinase M2 (PKM2) undergoes tyrosine phosphorylation and gives rise to the Warburg effect. The Warburg effect defines a pro-oncogenic metabolism switch such that cancer cells take up more glucose than normal tissue and favor incomplete oxidation of glucose, even in the presence of oxygen. Retinal photoreceptors are highly metabolic and their energy consumption is equivalent to that of a multiplying tumor cell. In the present study, we found that PKM2 is the predominant isoform in both rod- and cone-dominant retina, and that it undergoes a light-dependent tyrosine phosphorylation...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27879277/eukaryotic-translation-initiation-factor-5a2-promotes-metabolic-reprogramming-in-hepatocellular-carcinoma-cells
#4
Ting-Ting Cao, Shu-Hai Lin, Li Fu, Zhi Tang, Chi-Ming Che, Li-Yi Zhang, Xiao-Yan Ming, Teng-Fei Liu, Xu-Ming Tang, Bin-Bin Tan, Di Xiang, Feng Li, On-Yee Chan, Dan Xie, Zongwei Cai, Xin-Yuan Guan
Reprogramming of intracellular metabolism is common in liver cancer cells. Understanding the mechanisms of cell metabolic reprogramming may present a new basis for liver cancer treatment. In our previous study we reported that a novel oncogene eukaryotic translation initiation factor 5A2 (EIF5A2) promotes tumorigenesis under hypoxic condition. Here, we aim to investigate the role of EIF5A2 in cell metabolic reprogramming during hepatocellular carcinoma (HCC) development. In this study, we reported that the mRNA level of EIF5A2 was up-regulated in 59/105 (56...
November 22, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27875786/inflammation-dysregulated-metabolism-and-aromatase-in-obesity-and-breast-cancer
#5
REVIEW
Heba Zahid, Evan R Simpson, Kristy A Brown
Obesity is associated with an increased risk of estrogen-dependent breast cancer after menopause. Adipose tissue undergoes important changes in obesity due to excess storage of lipids, leading to adipocyte cell death and the recruitment of macrophages. The resultant state of chronic low-grade inflammation is associated with the activation of NFkB signaling and elevated levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis. This occurs not only in the visceral and subcutaneous fat, but also in the breast fat...
November 19, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27857021/effects-and-mechanisms-of-metformin-on-the-proliferation-of-esophageal-cancer-cells-in-vitro-and-in-vivo
#6
Jian-Cai Tang, Rui An, Yi-Qing Jiang, Jian Yang
Purpose: To observe the effects of metformin on human esophageal cancer cell, and to investigate its possible mechanisms. Materials and Methods: Cell viability was detected by using a cell counting kit-8(CCK-8), while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo...
November 11, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27856534/pkm2-cancer-metabolism-and-the-road-ahead
#7
REVIEW
Talya L Dayton, Tyler Jacks, Matthew G Vander Heiden
A major metabolic aberration associated with cancer is a change in glucose metabolism. Isoform selection of the glycolytic enzyme pyruvate kinase has been implicated in the metabolic phenotype of cancer cells, and specific pyruvate kinase isoforms have been suggested to support divergent energetic and biosynthetic requirements of cells in tumors and normal tissues. PKM2 isoform expression has been closely linked to embryogenesis, tissue repair, and cancer. In contrast, forced expression of the PKM1 isoform has been associated with reduced tumor cell proliferation...
December 2016: EMBO Reports
https://www.readbyqxmd.com/read/27826249/cannabinoid-cb1-receptors-are-localized-in-striated-muscle-mitochondria-and-regulate-mitochondrial-respiration
#8
Juan Mendizabal-Zubiaga, Su Melser, Giovanni Bénard, Almudena Ramos, Leire Reguero, Sergio Arrabal, Izaskun Elezgarai, Inmaculada Gerrikagoitia, Juan Suarez, Fernando Rodríguez De Fonseca, Nagore Puente, Giovanni Marsicano, Pedro Grandes
The cannabinoid type 1 (CB1) receptor is widely distributed in the brain and peripheral organs where it regulates cellular functions and metabolism. In the brain, CB1 is mainly localized on presynaptic axon terminals but is also found on mitochondria (mtCB1), where it regulates cellular respiration and energy production. Likewise, CB1 is localized on muscle mitochondria, but very little is known about it. The aim of this study was to further investigate in detail the distribution and functional role of mtCB1 in three different striated muscles...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27825133/foxo3a-confers-cetuximab-resistance-in-ras-wild-type-metastatic-colorectal-cancer-through-c-myc
#9
Yiyi Yu, Mengzhou Guo, Ye Wei, Shan Yu, Hong Li, Yan Wang, Xiaojing Xu, Yuehong Cui, Jiawen Tian, Li Liang, Ke Peng, Tianshu Liu
Resistance to epidermal growth factor receptor (EGFR) targeted monoclonal antibody therapy represents a clinical challenge in patients suffered from RAS wild-type (WT) metastatic colorectal cancer (mCRC). However, the molecular mechanisms and key factors conferring this resistance are largely unknown. Forkhead transcription factors of the O class 3a (FoxO3a), an important regulator of cell survival, has been reported with dual functions in tumor recently. In this study, we found that FoxO3a was highly expressed in cetuximab resistant CRC tissues compared with cetuximab sensitive tissues...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27822413/mir-106b-mediated-mfn2-suppression-is-critical-for-pkm2-induced-mitochondrial-fusion
#10
Haili Wu, Zhuoyu Li, Yingying Wang, Peng Yang, Zongrui Li, Hanqing Li, Changxin Wu
Cancer cells preferentially metabolize glucose through aerobic glycolysis. This phenomenon, known as the Warburg effect, is a characteristic of glucose metabolism in cancer cells. PKM2 is reported to imply an important role in glycolysis. However, whether and how PKM2 can cause mitochondrial dysfunction, then subsequently forcing cancer cells using glycolysis instead of oxidation phosphorylation is poorly understood. Here we reported that overexpression of PKM2 disrupted mitochondrial dynamics by enhancing fusion...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27821480/rbm4-regulates-neuronal-differentiation-of-mesenchymal-stem-cells-by-modulating-alternative-splicing-of-pyruvate-kinase-m
#11
Chun-Hao Su, Kuan-Yang Hung, Shih-Chieh Hung, Woan-Yuh Tarn
RBM4 promotes differentiation of neuronal progenitor cells and neurite outgrowth of cultured neurons via its role in splicing regulation. In this study, we further explored the role of RBM4 in neuronal differentiation. During neuronal differentiation, energy production shifts from glycolysis to oxidative phosphorylation. We found that the splice isoform change of the metabolic enzyme pyruvate kinase M (PKM) from PKM2 to PKM1 occurs during brain development and is impaired in RBM4-deficient brain. The PKM isoform change could be recapitulated in human mesenchymal stem cells (MSCs) during neuronal induction...
November 7, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27810895/a-novel-role-for-pyruvate-kinase-m2-as-a-corepressor-for-p53-during-the-dna-damage-response-in-human-tumor-cells
#12
Li Xia, Xin-Ran Wang, Xiao-Ling Wang, Su-Hui Liu, Xiao-Wei Ding, Guo-Qiang Chen, Ying Lu
The pyruvate kinase (PK) is a rate-limiting glycolytic enzyme catalyzing the dephosphorylation of phosphoenolpyruvate to pyruvate, yielding one molecule of ATP. The M2 isoform of PK (PKM2) is predominantly expressed in normal proliferating cells and tumors, and both metabolic and non-metabolic activities for the enzyme in promoting tumor cell proliferation have been identified. However, the exact roles of PKM2 in tumor initiation, growth and maintenance are not yet fully understood. Using immunoprecipitation-coupled LC-MS/MS in MCF7 cells exposed to DNA damaging agent, we report that the nuclear PKM2 interacts directly with P53 protein, a critical safeguard for genome stability...
November 3, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27805282/toll-like-receptor-3-stimulation-triggers-metabolic-reprogramming-in-pharyngeal-cancer-cell-line-through-myc-mapk-and-hif
#13
Tanja Matijevic Glavan, Ana Cipak Gasparovic, Benjamin Vérillaud, Pierre Busson, Jasminka Pavelic
Toll-like receptor 3 (TLR3) has a dual role in cancer; its activation can trigger apoptosis as well as stimulate cancer cell survival, proliferation, and progression. We have shown here that TLR3 activation can induce metabolic reprogramming in a pharyngeal cancer cell line, leading to increased aerobic glycolysis, cell migration, elevated levels of reactive oxidative species (ROS), and decreased anti-oxidative response. Key proteins in these signaling pathways are heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), pyruvate kinase M2 (PKM2), and CD44 variants, which were over-expressed after TLR3 stimulation...
November 2, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27801666/overexpression-of-pkm2-promotes-mitochondrial-fusion-through-attenuated-p53-stability
#14
Haili Wu, Peng Yang, Wanglai Hu, Yingying Wang, Yangxu Lu, Lichao Zhang, Yongsheng Fan, Hong Xiao, Zhuoyu Li
M2-type pyruvate kinase (PKM2) contributes to the Warburg effect. However, it remains unknown as to whether PKM2 has an inhibitory effect on mitochondrial function. We report in this work that PKM2 overexpression inhibits the expression of Drp1 and results in the mitochondrial fusion. The ATP production was found to be decreased, the mtDNA copy number elevated and the expression level of electron transport chain (ETC) complex I, III, V depressed in PKM2 overexpressed cells. PKM2 overexpression showed a decreased p53 protein level and a shorter p53 half-life...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27785603/linc-ror-confers-gemcitabine-resistance-to-pancreatic-cancer-cells-via-inducing-autophagy-and-modulating-the-mir-124-ptbp1-pkm2-axis
#15
Chenggang Li, Zhiming Zhao, Zhipeng Zhou, Rong Liu
PURPOSE: In this study, we investigated the regulation of linc-ROR on autophagy and gemcitabine resistance of pancreatic cancer cells and further studied the underlying involvement of the miR-124/PTBP1/PKM2 axis in this regulation. METHODS: Pancreatic cancer cell lines PANC-1 and MIAPaCa-2 cells were used as in vitro model. Autophagy was assessed by western blot of LC3 I/II and observation GFP-LC3 puncta. Cell viability was examined using CCK-8 assay. Cell apoptosis was examined by flow cytometric analysis of Annexin V/PI staining...
October 26, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27779186/pkm2-dependent-glycolysis-promotes-nlrp3-and-aim2-inflammasome-activation
#16
Min Xie, Yan Yu, Rui Kang, Shan Zhu, Liangchun Yang, Ling Zeng, Xiaofang Sun, Minghua Yang, Timothy R Billiar, Haichao Wang, Lizhi Cao, Jianxin Jiang, Daolin Tang
Sepsis, severe sepsis and septic shock are the main cause of mortality in non-cardiac intensive care units. Immunometabolism has been linked to sepsis; however, the precise mechanism by which metabolic reprogramming regulates the inflammatory response is unclear. Here we show that aerobic glycolysis contributes to sepsis by modulating inflammasome activation in macrophages. PKM2-mediated glycolysis promotes inflammasome activation by modulating EIF2AK2 phosphorylation in macrophages. Pharmacological and genetic inhibition of PKM2 or EIF2AK2 attenuates NLRP3 and AIM2 inflammasomes activation, and consequently suppresses the release of IL-1β, IL-18 and HMGB1 by macrophages...
October 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27775792/mir-143-is-involved-in-endothelial-cell-dysfunction-through-suppression-of-glycolysis-and-correlated-with-atherosclerotic-plaques-formation
#17
R-H Xu, B Liu, J-D Wu, Y-Y Yan, J-N Wang
OBJECTIVE: Atherosclerosis is recognized as a chronic inflammatory disease leading to hardening of the vessel wall and narrowing of arteries. Endothelial cells (ECs) exhibit highly active glycolysis, the dysfunction of which leads to accumulation of lipids in the arterial wall and formation of atherosclerotic plaque. MATERIALS AND METHODS: qRT-PCR was performed to compare the deregulated miR-143 between atherosclerotic plaque and normal vessel tissues. The direct target of miR-143 was verified by Western blot and luciferase assay...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27769315/leptin-promotes-epithelial-mesenchymal-transition-of-breast-cancer-via-the-upregulation-of-pyruvate-kinase-m2
#18
Lan Wei, Kuangfa Li, Xueli Pang, Bianqin Guo, Min Su, Yunxiu Huang, Nian Wang, Feihu Ji, Changli Zhong, Junhong Yang, Zhiqian Zhang, Yulin Jiang, Yifeng Liu, Tingmei Chen
BACKGROUND: Accumulating researches have shown that epithelial-mesenchymal transition (EMT) contributes to tumor metastasis. Leptin, a key adipokine secreted from adipocytes, shapes the tumor microenvironment, potentiates the migration of breast cancer cells and angiogenesis, and is also involved in EMT. However, the potential mechanism remains unknown. This study aims to explore the effect of leptin on EMT in breast cancer cells and the underlying mechanism. METHODS: With the assessment of EMT-associated marker expression in MCF-7, SK-BR-3, and MDA-MB-468 cells, the effect of leptin on breast cancer cells was analyzed...
October 21, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27750035/participation-of-hifs-in-the-regulation-of-sertoli-cell-lactate-production
#19
María Noel Galardo, Agostina Gorga, Joaquín Pedro Merlo, Mariana Regueira, Eliana Herminia Pellizzari, Selva Beatriz Cigorraga, María Fernanda Riera, Silvina Beatriz Meroni
Hypoxia Inducible Factors (HIFs) are master regulators of glycolytic metabolism. HIFs consist of a constitutive HIFbeta (HIFβ) subunit and a HIFalpha (HIFα) subunit, whose half-life depends on prolyl-hydroxylases activity. Inhibition of prolyl-hydroxylases by hypoxia or transition metals, or augmentation of HIFα subunit levels by hormonal stimuli lead to a higher HIF transcriptional activity. On the other hand, it is well known that lactate produced by Sertoli cells is delivered to and used by germ cells as an energy substrate...
October 14, 2016: Biochimie
https://www.readbyqxmd.com/read/27743386/correlation-between-three-glycometabolic-related-hormones-and-muscle-glycolysis-as-well-as-meat-quality-in-three-pig-breeds
#20
Jia Luo, Yuan L Shen, Gang H Lei, Ping K Zhu, Zhi Y Jiang, Lin Bai, Zhou M Li, Qing G Tang, Wei X Li, Hua S Zhang, Li Zhu
BACKGROUND: The present study aimed to evaluate the correlations among muscle concentrations of three glycometabolic-related hormones (insulin, epinephrine and glucagon), muscle glycolysis and meat quality in representative muscles of either glycolytic or oxidative types. Moreover, the relative glycometabolic-related gene expression was measured. One Western crossbreed DLY (Duroc × (Landrace × Yorkshire)), one crossbreed with half-Chinese native-pig origin DL (Duroc × LiangShan) and one pure Chinese native pig TP (Tibetan pig) were used in the present study...
October 15, 2016: Journal of the Science of Food and Agriculture
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