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https://www.readbyqxmd.com/read/29113354/6-phosphofructo-2-kinase-fructose-2-6-bisphosphatase-isoform-3-spatially-mediates-autophagy-through-the-ampk-signaling-pathway
#1
Siyuan Yan, Xiaoli Wei, Shanshan Xu, Hui Sun, Weijun Wang, Ling Liu, Xuejun Jiang, Yongxiang Zhang, Yongsheng Che
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), is a critical enzyme for glycolysis and highly expressed in cancer cells. It plays an essential role in regulating metabolism, angiogenesis, and inflammation. Although PFKFB3 is involved in modulating autophagy, its regulatory role appears to be either positive or negative, which remains to be clarified. Unlike other PFK-2/FBPase isoforms, PFKFB3 can localize in both nucleus and cytoplasm, leading to the speculation that subcellular localization of PFKFB3 may play a regulatory role in autophagy...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29101015/dna-damage-metabolism-and-aging-in-pro-inflammatory-t-cells-rheumatoid-arthritis-as-a-model-system
#2
REVIEW
Yinyin Li, Jörg J Goronzy, Cornelia M Weyand
The aging process is the major driver of morbidity and mortality, steeply increasing the risk to succumb to cancer, cardiovascular disease, infection and neurodegeneration. Inflammation is a common denominator in age-related pathologies, identifying the immune system as a gatekeeper in aging overall. Among immune cells, T cells are long-lived and exposed to intense replication pressure, making them sensitive to aging-related abnormalities. In successful T cell aging, numbers of naïve cells, repertoire diversity and activation thresholds are preserved as long as possible; in maladaptive T cell aging, protective T cell functions decline and pro-inflammatory effector cells are enriched...
November 8, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29072034/potential-effect-of-exercise-in-ameliorating-insulin-resistance-at-transcriptome-level
#3
Zhigang Hu, Lei Zhou, Tingting He
BACKGROUND: Insulin resistance can lead to the pathogenesis of type 2 diabetes and exercise can increase insulin sensitivity. And different exercises may have different influences on the mitigation of insulin resistance. It's still unclear how exercise affects inherited insulin resistance at transcriptome level. The purpose of our study was to analyze the potential effects of exercise in ameliorating insulin resistance at transcriptome level. METHODS: Herein, we analyzed two skeletal muscle transcriptome profiles, including gene profiles between inherited insulin resistant patients and matched healthy controls, and between trained and sedentary subjects (young and old subjects, respectively)...
October 24, 2017: Journal of Sports Medicine and Physical Fitness
https://www.readbyqxmd.com/read/29061364/inflammatory-microglia-are-glycolytic-and-iron-retentive-and-typify-the-microglia-in-app-ps1-mice
#4
R Holland, A L McIntosh, O M Finucane, V Mela, A Rubio-Araiz, G Timmons, S A McCarthy, Y K Gun'ko, M A Lynch
Microglia, like macrophages, can adopt inflammatory and anti-inflammatory phenotypes depending on the stimulus. In macrophages, the evidence indicates that these phenotypes have different metabolic profiles with lipopolysaccharide (LPS)- or interferon-γ (IFNγ)-stimulated inflammatory cells switching to glycolysis as their main source of ATP and interleukin-4 (IL-4)-stimulated cells utilizing oxidative phosphorylation. There is a paucity of information regarding the metabolic signatures of inflammatory and anti-inflammatory microglia...
October 20, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28977989/the-molecular-basis-of-targeting-pfkfb3-as-a-therapeutic-strategy-against-cancer
#5
Luo Lu, Yaoyu Chen, Yu Zhu
6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatases (PFKFBs) are bifunctional enzymes which regulate the transformation between fructose-2, 6-bisphosphate (F2, 6BP) and fructose-6-phosphate (F6P) in the process of glucose metabolism. Among the four isozymes (PFKFB1-4), PFKFB3 has stronger kinase activity than phosphatase activity, resulting in the synthesis of F2, 6BP and the promotion of glycolysis. Additionally, PFKFB3 plays a key role in cell cycle regulation. It has been confirmed that PFKFB3 is upregulated in a variety of tumor cells, and inhibition of it results in suppression of the growth of tumor cells by downregulating the glycolytic flux...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28963395/lncrna-wires-up-hippo-and-hedgehog-signaling-to-reprogramme-glucose-metabolism
#6
Xin Zheng, Han Han, Guang-Ping Liu, Yan-Xiu Ma, Ruo-Lang Pan, Ling-Jie Sang, Rui-Hua Li, Luo-Jia Yang, Jeffrey R Marks, Wenqi Wang, Aifu Lin
The Hippo pathway plays essential roles in organ size control and cancer prevention via restricting its downstream effector, Yes-associated protein (YAP). Previous studies have revealed an oncogenic function of YAP in reprogramming glucose metabolism, while the underlying mechanism remains to be fully clarified. Accumulating evidence suggests long noncoding RNAs (lncRNAs) as attractive therapeutic targets, given their roles in modulating various cancer-related signaling pathways. In this study, we report that lncRNA breast cancer anti-estrogen resistance 4 (BCAR4) is required for YAP-dependent glycolysis...
September 28, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28945981/a-high-throughput-screening-triage-workflow-to-authenticate-a-novel-series-of-pfkfb3-inhibitors
#7
Stephen A St-Gallay, Neil Bennett, Susan E Critchlow, Nicola Curtis, Gareth Davies, Judit Debreczeni, Nicola Evans, Ian Hardern, Geoff Holdgate, Neil P Jones, Lindsey Leach, Sarita Maman, Sheila McLoughlin, Marian Preston, Laurent Rigoreau, Andrew Thomas, Andrew P Turnbull, Graeme Walker, Jarrod Walsh, Richard A Ward, Ed Wheatley, Jon Winter-Holt
A high-throughput screen (HTS) of human 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) resulted in several series of compounds with the potential for further optimization. Informatics was used to identify active chemotypes with lead-like profiles and remove compounds that commonly occurred as actives in other HTS screens. The activities were confirmed with IC50 measurements from two orthogonal assay technologies, and further analysis of the Hill slopes and comparison of the ratio of IC50 values at 10 times the enzyme concentration were used to identify artifact compounds...
September 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28935506/endothelial-specific-sirt3-deletion-impairs-glycolysis-and-angiogenesis-and-causes-diastolic-dysfunction
#8
Xiaochen He, Heng Zeng, Sean T Chen, Richard J Roman, Judy L Aschner, Sean Didion, Jian-Xiong Chen
Endothelial glycolysis plays a critical role in the regulation of angiogenesis. We investigated the role of Sirtuin 3 (SIRT3) on endothelial cell (EC) glycolytic metabolism, angiogenesis, and diastolic function. Our aim was to test the hypothesis that loss of SIRT3 in ECs impairs endothelial glycolytic metabolism and angiogenesis and contributes to myocardial capillary rarefaction and the development of diastolic dysfunction. Using SIRT3 deficient ECs, SIRT3 was found to regulate a metabolic switch between mitochondrial respiration and glycolysis...
November 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28875379/tumor-vessel-disintegration-by-maximum-tolerable-pfkfb3-blockade
#9
Lena-Christin Conradi, Aleksandra Brajic, Anna Rita Cantelmo, Ann Bouché, Joanna Kalucka, Andreas Pircher, Ulrike Brüning, Laure-Anne Teuwen, Stefan Vinckier, Bart Ghesquière, Mieke Dewerchin, Peter Carmeliet
Blockade of the glycolytic activator PFKFB3 in cancer cells (using a maximum tolerable dose of 70 mg/kg of the PFKFB3 blocker 3PO) inhibits tumor growth in preclinical models and is currently being tested as a novel anticancer treatment in phase I clinical trials. However, a detailed preclinical analysis of the effects of such maximum tolerable dose of a PFKFB3 blocker on the tumor vasculature is lacking, even though tumor endothelial cells are hyper-glycolytic. We report here that a high dose of 3PO (70 mg/kg), which inhibits cancer cell proliferation and reduces primary tumor growth, causes tumor vessel disintegration, suppresses endothelial cell growth for protracted periods, (model-dependently) aggravates tumor hypoxia, and compromises vascular barrier integrity, thereby rendering tumor vessels more leaky and facilitating cancer cell intravasation and dissemination...
November 2017: Angiogenesis
https://www.readbyqxmd.com/read/28875330/liposomes-co-loaded-with-6-phosphofructo-2-kinase-fructose-2-6-biphosphatase-3-pfkfb3-shrna-plasmid-and-docetaxel-for-the-treatment-of-non-small-cell-lung-cancer
#10
Nusrat Chowdhury, Imran Vhora, Ketan Patel, Ravi Doddapaneni, Arindam Mondal, Mandip Singh
PURPOSE: Non-small cell lung cancer is the leading cause of cancer related deaths globally. Considering the side effects and diminishing chemosensitivity to chemotherapy, novel treatment approaches are sought. Hence, we aim to develop a liposomal co-delivery system of pDNA expressing shRNA against PFKFB3 (pshPFKFB3) and docetaxel (DTX). METHODS: Cationic DTX liposomes complexed with pshPFKFB3 (PSH-DL) were developed. In vitro cell line studies were performed to evaluate transfection, PFKFB3 mRNA silencing, cytotoxicity, pGP inhibition, and protein markers expression...
November 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28857200/by-inhibiting-pfkfb3-aspirin-overcomes-sorafenib-resistance-in-hepatocellular-carcinoma
#11
Sainan Li, Weiqi Dai, Wenhui Mo, Jingjing Li, Jiao Feng, Liwei Wu, Tong Liu, Qiang Yu, Shizan Xu, Wenwen Wang, Xiya Lu, Qinghui Zhang, Kan Chen, Yujing Xia, Jie Lu, Yingqun Zhou, Xiaoming Fan, Ling Xu, Chuanyong Guo
Hepatocellular carcinoma (HCC) is one of the few cancers with a continuous increase in incidence and mortality. Drug resistance is a major problem in the treatment of HCC. In this study, two sorafenib-resistant HCC cell lines and a nude mouse subcutaneously tumor model were used to explore the possible mechanisms leading to sorafenib resistance, and to investigate whether aspirin could increase the sensitivity of hepatoma cells to sorafenib. The combination of aspirin and sorafenib resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo...
December 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28834297/tgf-%C3%AE-1-targets-smad-p38-mapk-and-pi3k-akt-signaling-pathways-to-induce-pfkfb3-gene-expression-and-glycolysis-in-glioblastoma-cells
#12
Ana Rodríguez-García, Paula Samsó, Pere Fontova, Helga Simon-Molas, Anna Manzano, Esther Castaño, Jose Luis Rosa, Ubaldo Martinez-Outshoorn, Francesc Ventura, Àurea Navarro-Sabaté, Ramon Bartrons
In human cancers, transforming growth factor-β1 (TGF-β1) plays a dual role by acting as both a tumor suppressor and a promoter of tumor metastasis. Although TGF-β1 contributes to the metabolic reprogramming of cancer cells and tumor-associated stromal cells, little is known of the molecular mechanisms connecting this cytokine with enhanced glycolysis. PFKFB3 is a homodymeric bifunctional enzyme, belonging to the family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases, that controls the conversion of fructose-6-phosphate (Fru-6-P) to fructose-2,6-bisphosphate (Fru-2,6-P2 )...
October 2017: FEBS Journal
https://www.readbyqxmd.com/read/28765514/the-molecular-basis-of-targeting-pfkfb3-as-a-therapeutic-strategy-against-cancer
#13
REVIEW
Luo Lu, Yaoyu Chen, Yu Zhu
6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatases (PFKFBs) are bifunctional enzymes which regulate the transformation between fructose-2, 6-bisphosphate (F2, 6BP) and fructose-6-phosphate (F6P) in the process of glucose metabolism. Among the four isozymes (PFKFB1-4), PFKFB3 has stronger kinase activity than phosphatase activity, resulting in the synthesis of F2, 6BP and the promotion of glycolysis. Additionally, PFKFB3 plays a key role in cell cycle regulation. It has been confirmed that PFKFB3 is upregulated in a variety of tumor cells, and inhibition of it results in suppression of the growth of tumor cells by downregulating the glycolytic flux...
July 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28762754/flow-responsive-vascular-endothelial-growth-factor-receptor-protein-kinase-c-isoform-epsilon-signaling-mediates-glycolytic-metabolites-for-vascular-repair
#14
Kyung In Baek, Rongsong Li, Nelson Jen, Howard Choi, Amir Kaboodrangi, Peipei Ping, David Liem, Tyler Beebe, Tzung K Hsiai
AIMS: Hemodynamic shear stress participates in maintaining vascular redox status. Elucidating flow-mediated endothelial metabolites enables us to discover metabolic biomarkers and therapeutic targets. We posited that flow-responsive vascular endothelial growth factor receptor (VEGFR)-protein kinase C isoform epsilon (PKCɛ)-6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) signaling modulates glycolytic metabolites for vascular repair. RESULTS: Bidirectional oscillatory flow (oscillatory shear stress [OSS]: 0...
September 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28644415/genome-wide-association-study-of-dietary-pattern-scores
#15
Frédéric Guénard, Annie Bouchard-Mercier, Iwona Rudkowska, Simone Lemieux, Patrick Couture, Marie-Claude Vohl
Dietary patterns, representing global food supplies rather than specific nutrients or food intakes, have been associated with cardiovascular disease (CVD) incidence and mortality. The contribution of genetic factors in the determination of food intakes, preferences and dietary patterns has been previously established. The current study aimed to identify novel genetic factors associated with reported dietary pattern scores. Reported dietary patterns scores were derived from reported dietary intakes for the preceding month and were obtained through a food frequency questionnaire and genome-wide association study (GWAS) conducted in a study sample of 141 individuals...
June 23, 2017: Nutrients
https://www.readbyqxmd.com/read/28576491/blockage-of-glycolysis-by-targeting-pfkfb3-alleviates-sepsis-related-acute-lung-injury-via-suppressing-inflammation-and-apoptosis-of-alveolar-epithelial-cells
#16
Yuanqi Gong, Haibing Lan, Zhihong Yu, Meng Wang, Shu Wang, Yu Chen, Haiwei Rao, Jingying Li, Zhiyong Sheng, Jianghua Shao
Sepsis-related acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells resulting in acute hypoxemic respiratory failure. Recent studies indicated that anaerobic glycolysis play an important role in sepsis. However, whether inhibition of aerobic glycolysis exhibits beneficial effect on sepsis-induced ALI is not known. In vivo, a cecal ligation and puncture (CLP)-induced ALI mouse model was set up and mice treated with glycolytic inhibitor 3PO after CLP...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28571757/hmgb1-promotes-hlf-1-proliferation-and-ecm-production-through-activating-hif1-%C3%AE-regulated-aerobic-glycolysis
#17
JianNing Xu, JingYing Li, ZhiHong Yu, HaiWei Rao, Shu Wang, HaiBing Lan
Aerobic glycolysis is a crucial event in fibroblast differentiation, and extracellular matrix (ECM) production in the progression of pulmonary fibrosis (PF). Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of PF. However, whether aerobic glycolysis contributes to HMGB1-induced fibroblast proliferation and ECM production in PF has not yet been determined. In this study, we investigated the effects of HMGB1 on human embryonic lung fibroblast (HLF-1) proliferation, ECM production, and aerobic glycolysis...
August 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28559290/a-role-for-pfkfb3-ipfk2-in-metformin-suppression-of-adipocyte-inflammatory-responses
#18
Ting Qi, Yanming Chen, Honggui Li, Ya Pei, Shih-Lung Woo, Xin Guo, Jiajia Zhao, Xiaoxian Qian, Joseph Awika, Yuqing Huo, Chaodong Wu
Metformin improves obesity-associated metabolic dysregulation, but has controversial effects on adipose tissue inflammation. The objective of the study is to examine the direct effect of metformin on adipocyte inflammatory responses and elucidate the underlying mechanisms. Adipocytes were differentiated from 3T3-L1 cells and treated with metformin at various doses and for different time periods. The treated cells were examined for the proinflammatory responses, as well as the phosphorylation states of AMPK and the expression of PFKFB3/iPFK2...
July 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28395898/p63-adjusts-sugar-taste-of-epidermal%C3%A2-layers
#19
REVIEW
Ivano Amelio, Gerry Melino, Eleonora Candi
p63 is a master regulator of epidermal biology, sustaining stemness and renewal capacity of the proliferating keratinocyte compartment. Hamanaka and Mutlu propose that p63 regulates the keratinocyte proliferation/differentiation switch by affecting the cellular glycolic rate through a direct transcriptional regulation of the metabolic enzyme PFKFB3. This finding sheds light on mechanisms underlining p63 function in the skin and suggests a role for energetic metabolism in epidermal biology.
June 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28348059/the-glycolytic-enzyme-pfkfb3-is-involved-in-estrogen-mediated-angiogenesis-via-gper1
#20
Annalisa Trenti, Serena Tedesco, Carlotta Boscaro, Nicola Ferri, Andrea Cignarella, Lucia Trevisi, Chiara Bolego
The endogenous estrogen 17β-estradiol (E2) is a key factor in promoting endothelial healing and angiogenesis. Recently, proangiogenic signals including vascular endothelial growth factor and others have been shown to converge in endothelial cell metabolism. Because inhibition of the glycolytic enzyme activator phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) reduces pathologic angiogenesis and estrogen receptor (ER) signaling stimulates glucose uptake and glycolysis by inducing PFKFB3 in breast cancer, we hypothesized that E2 triggers angiogenesis in endothelial cells via rapid ER signaling that requires PFKFB3 as a downstream effector...
June 2017: Journal of Pharmacology and Experimental Therapeutics
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