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Shuhei Kuwabara, Misato Yamaki, Huiqing Yu, Motoyuki Itoh
Glycolysis, the classic pathway for producing energy, has been known to be involved in neural development. Notch signaling also contributes to neural development and regulation of glycolysis in various tissues. However, the role of Notch signaling in glycolysis-related gene regulation during neural development is poorly understood. Here, we analyzed mRNA expression patterns and levels of glucose transporters (GLUT) as well as rate-limiting enzymes in glycolysis using zebrafish mib1ta52b mutants, in which Notch signaling was deficient at the early embryonic and larval stages...
June 15, 2018: Biochemical and Biophysical Research Communications
Vered Behar, Hadas Pahima, Adi Kozminsky-Atias, Nir Arbel, Emmanuel Loeb, Max Herzberg, Oren M Becker
Overexpression of hexokinase 2 (HK2), and its binding to VDAC1 on the outer mitochondrial membrane of cancer cells, is key to their metabolic reprogramming to aerobic glycolysis, which enables them to proliferate. We describe Comp-1, an allosteric small molecule that selectively detaches HK2 from the mitochondria. Detachment of HK2 reduces glycolysis and triggers apoptosis in cancer cells, without affecting HK1 expressing normal cells. The anti-cancer activity of Comp-1 was demonstrated in the UVB-damaged skin model in SKH-1 mice...
June 13, 2018: Journal of Investigative Dermatology
Yingchun Qiao, Xixi Tian, Li Men, Shengyu Li, Yufeng Chen, Meiting Xue, Yahui Hu, Pengfei Zhou, Guangfeng Long, Yue Shi, Ruiqing Liu, Yunde Liu, Zhi Qi, Yujie Cui, Yanna Shen
Diabetic nephropathy (DN) is a serious complication of diabetes and can cause an increased mortality risk. It was previously reported that NLR family pyrin domain containing 3 (NLRP3) inflammasome is involved in the pathogenesis of diabetes. However, the underlying mechanism is not clearly understood. In the present study, the effects of spleen tyrosine kinase (Syk) and c‑Jun N‑terminal kinase (JNK) on the NLRP3 inflammasome were examined in vivo and in vitro. Sprague‑Dawley rats were injected intraperitoneally with streptozotocin (65 mg/kg) to induce diabetes...
June 14, 2018: Molecular Medicine Reports
Mingliang Wang, Wendong Wang, Jiashun Wang, Jun Zhang
OBJECTIVE: This study aims to demonstrate the role of miR-182 in the glucose metabolism of NSCLC cells and the potential mechanism. METHODS: MTT Cytotoxicity Assay was used to measure the function of differentially expressed miR-182 on two NSCLC cell lines proliferation. Metabolite analysis was introduced to monitor the glucose consumption, lactate release and glycolytic intermediate metabolites. The mRNA level of critical genes involved in glycolysis was detected by qRT-PCR...
June 9, 2018: Biochemical and Biophysical Research Communications
Mateus Mota, William P Jackson, Sarah K Bailey, Praveen Vayalil, Aimee Landar, Jack W Rostas, Madhuri S Mulekar, Rajeev S Samant, Lalita A Shevde
The NF2 gene encodes the tumor and metastasis suppressor protein Merlin. Merlin exerts its tumor suppressive role by inhibiting proliferation and inducing contact-growth inhibition and apoptosis. In the current investigation, we determined that loss of Merlin in breast cancer tissues is concordant with the loss of the inhibitory SMAD, SMAD7, of the TGF-β pathway. This was reflected as dysregulated activation of TGF-β signaling that co-operatively engaged with effectors of the Hippo pathway (YAP/TAZ/TEAD)...
June 9, 2018: Carcinogenesis
Kejian Zhang, Mingrui Zhang, Hui Jiang, Fenglin Liu, Hongwei Liu, Yang Li
Glycolysis is a metabolic pathway that is enhanced in cancer cells. miR-214 plays an important role in cancer development and can modulate glycolysis. However, whether miR-214 can regulate glycolysis in non-small-cell lung cancer (NSCLC) cells has not yet been investigated. The expression levels of miR-214 in 7 NSCLC cell lines were measured by qRT-PCR. MTT assay was performed to evaluate the cell proliferation. Glucose consumption and lactate production were measured to assess the level of glycolysis. The expression of hexokinase 2 (HK2) and pyruvate kinase isozyme M2 (PKM2) was measured by qRT-PCR and western blot analysis...
June 6, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Shili Xu, Arthur Catapang, Hanna M Doh, Nicholas A Bayley, Jason T Lee, Daniel Braas, Thomas G Graeber, Harvey R Herschman
Although absent in most adult tissues, hexokinase 2 (HK2) is expressed in a majority of tumors and contributes to increased glucose consumption and to in vivo tumor 18 F-FDG PET signaling. Methods: Both HK2 knockdown and knockout approaches were used to investigate the role of HK2 in cancer cell proliferation, in vivo xenograft tumor progression and 18 F-FDG tumor accumulation. BioProfiler analysis monitored cell culture glucose consumption and lactate production; 18 F-FDG PET/CT monitored in vivo tumor glucose accumulation...
June 7, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Leshan Wang, Lv Luo, Zhao Weijie, Kelin Yang, Gang Shu, Songbo Wang, Ping Gao, Xiaotong Zhu, Qian-Yun Xi, Yongliang Zhang, Qingyan Jiang, Lina Wang
Lauric acid (LA), which is the primary fatty acid in coconut oil, was reported to have many metabolic benefits. TLR4 is a common receptor of lipopolysaccharides and involved mainly in inflammation responses. Here, we focused on the effects of LA on skeletal muscle fiber types and metabolism. We found that 200μM LA treatment in C2C12 or dietary supplementation of 1% LA increased MHCIIb protein expression and the proportion of type IIb muscle fibers from 0.452 ± 0.0165 to 0.572 ± 0.0153, increasing the mRNA expression of genes involved in glycolysis, such as HK2 and LDH2 (from 1...
June 7, 2018: Journal of Agricultural and Food Chemistry
Emmanuel J Camus, Luc Van Overstraeten
Displaced fractures of the distal radius often require reduction and fixation to improve outcome in active patients. The volar locking plate gained ground over pinning, which was the first surgical solution described. But pinning methods have since evolved with fewer complications. The authors present a clinical study of distal radius fracture fixation using the HK2 technique, where subchondral pins are connected to intra-focal pins. The results are satisfactory with a lower complication rate compared to other pinning methods...
June 5, 2018: European Journal of Orthopaedic Surgery & Traumatology: Orthopédie Traumatologie
Lian Hui, Jingru Zhang, Xing Guo
Laryngeal squamous cell carcinoma (LSCC) is the most common form of laryngeal carcinoma with poor prognosis. Exploring novel factors involved in the progression of LSCC is quite necessary for understanding the mechanisms and designing therapeutic strategies for LSCC. In this study, we showed that miR-125b-5p was significantly down-regulated in LSCC tissues and cell lines. The decreased expression of miR-125b-5p was associated with the tumor differentiation, metastasis and high clinical stage of the LSCC patients...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hiroko Hamatani, Toru Sakairi, Hidekazu Ikeuchi, Yoriaki Kaneko, Akito Maeshima, Yoshihisa Nojima, Keiju Hiromura
BACKGROUND: Wilms' tumor 1 (WT1) is essential for normal podocyte function. Previous reports have shown that the WT1 promoter is often methylated in cancers, leading to transcriptional silencing. Transforming growth factor-β1 (TGF-β1) is reported to downregulate WT1 expression in podocytes. Based on the hypothesis that epigenetic modification plays a role in this process, we examined whether TGF-β1 affects the methylation status of WT1 regulatory regions. METHODS: Conditional immortalized human podocytes were treated with TGF-β1...
May 30, 2018: Nephrology
Lolita Petit, Shan Ma, Joris Cipi, Shun-Yun Cheng, Marina Zieger, Nissim Hay, Claudio Punzo
Aerobic glycolysis accounts for ∼80%-90% of glucose used by adult photoreceptors (PRs); yet, the importance of aerobic glycolysis for PR function or survival remains unclear. Here, we further established the role of aerobic glycolysis in murine rod and cone PRs. We show that loss of hexokinase-2 (HK2), a key aerobic glycolysis enzyme, does not affect PR survival or structure but is required for normal rod function. Rods with HK2 loss increase their mitochondrial number, suggesting an adaptation to the inhibition of aerobic glycolysis...
May 29, 2018: Cell Reports
Dong Wang, Qingjie Wang, Gaoliang Yan, Yong Qiao, Boqian Zhu, Bo Liu, Chengchun Tang
The mitochondrial pyruvate carrier (MPC) complex, located on the inner mitochondrial membrane, transports pyruvate to the mitochondrial matrix for oxidative phosphorylation. Previous studies have shown that the MPC complex is a key regulator of glycolysis in tumor cells. The present study evaluated the role of the MPC under hypoxic conditions in human umbilical vein endothelial cells, which rely on glycolysis for energy generation. It was indicated that hypoxia led to an increase in lactate secretion and a decrease in MPC1 and MPC2 levels, which were upregulated following re‑oxygenation...
May 29, 2018: Molecular Medicine Reports
Jian Ma, Yanxin Fan, Tingting Feng, Fangjun Chen, Zhipeng Xu, Suqing Li, Qingfeng Lin, Xiaoting He, Weihong Shi, Yang Liu, Zhihua Liu, Bin Zhu, Xiufeng Cao
[This corrects the article DOI: 10.18632/oncotarget.21195.].
May 4, 2018: Oncotarget
Paola Pontrelli, Annarita Oranger, Mariagrazia Barozzino, Chiara Divella, Francesca Conserva, Maria Grazia Fiore, Roberta Rossi, Massimo Papale, Giuseppe Castellano, Simona Simone, Luigi Laviola, Francesco Giorgino, Domenico Piscitelli, Anna Gallone, Loreto Gesualdo
Diabetic nephropathy patients (DN) are characterized by increased lysine63 ubiquitination (Lys63-Ub) at the tubular level. Autophagy is deregulated under diabetic conditions, even though the molecular mechanisms and the consequences of this alteration need to be elucidated. The aim of this study was to investigate the link between Lys63-Ub and autophagy in DN and the involvement of these two processes in tubular cell fate. Immunohistochemistry of beclin-1, LC3, and p62 on kidney biopsies highlighted increased protein expression of all these autophagic factors at the tubular level in DN compared to other nephritis...
May 27, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Junyan Jin, Yunxia Yang, Xiaoming Zhu, Dong Han, Haokun Liu, Shouqi Xie
We compared the glucose clearance ability of gibel carp CAS III (A strain) with gibel carp Dongting (DT strain). A previous study suggested that these two strains responded to insulin differently. As insulin plays an important role in glucose utilization, we hypothesized that the ability to eliminate excess glucose after a glucose load would differ between A strain and DT strain. To test this hypothesis, fasted specimens of both strains of gibel carp were injected with glucose. As expected, glucose induced hyperglycemia in both A strain and DT strain...
May 23, 2018: General and Comparative Endocrinology
Robert Kleszcz, Jarosław Paluszczak, Violetta Krajka-Kuźniak, Wanda Baer-Dubowska
BACKGROUND: Cancer cells are dependent on aerobic glycolysis for energy production and increased glutamine consumption. HIF-1α and c-MYC transcription factors regulate the expression of glycolytic and glutaminolytic genes. Their activity may be repressed by SIRT6. Head and neck carcinomas show frequent activation of c-MYC function and SIRT6 down-regulation, which contributes to a strong dependence on glucose and glutamine availability. OBJECTIVES: The aim of this study was to compare the influence of HIF-1α and c-MYC inhibitors (KG-548 and 10058-F4, respectively) and potential SIRT6 inducers - resveratrol and its synthetic derivative DMU-212 with the effect of glycolysis and glutaminolysis inhibitors (2-deoxyglucose and aminooxyacetic acid, respectively) on the metabolism and expression of metabolic enzymes in FaDu hypopharyngeal carcinoma cells...
May 17, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Trudy McGarry, Carl Orr, Sarah Wade, Monika Biniecka, Siobhan Wade, Lorna Gallagher, Candice Low, Douglas J Veale, Ursula Fearon
OBJECTIVE: To examine the effect of tofacitinib on metabolic activity, mitochondrial function and pro-inflammatory mechanisms in Rheumatoid Arthritis. METHODS: Ex-vivo RA synovial explants and primary RA synovial fibroblasts (RAFLS) were cultured with tofacitinib (1μM). RAFLS bioenergetics was assessed using the XF24-Flux-analyser, and key metabolic genes by real-time PCR. Mitochondrial function was assessed using specific cell fluorescent probes and by mitochondrial gene arrays...
May 23, 2018: Arthritis & Rheumatology
Changhua Zhuo, Xianyi Wu, Jing Li, Dan Hu, Jinliang Jian, Changjiang Chen, Xiongwei Zheng, Chunkang Yang
Chemokine (C-X-C motif) ligand 1 (CXCL1) is a chemotactic cytokine known to regulate cancer progression and invasion. However, the prognostic significance of CXCL1 expression in colorectal cancer (CRC) has not been fully characterized. This study explored the clinicopathological significance and potential role of CXCL1 in the carcinogenesis and progression of CRC. The protein expression of CXCL1 was measured immunohistochemically in tissue microarrays constructed from 276 CRC patients. CXCL1 expression levels and their associations with clinicopathological characteristics and patient survival were evaluated...
May 21, 2018: Bioscience Reports
Olivier Blanchard, Bisera Stepanovska, Manuel Starck, Martin Erhardt, Isolde Römer, Dagmar Meyer Zu Heringdorf, Josef Pfeilschifter, Uwe Zangemeister-Wittke, Andrea Huwiler
Sphingosine kinase (SK) catalyses the formation of sphingosine 1-phosphate (S1P), which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ) induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF) and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated...
May 17, 2018: International Journal of Molecular Sciences
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