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Tesfaye W Tefera, Karin Borges
Although alterations in energy metabolism are known in ALS, the specific mechanisms leading to energy deficit are not understood. We measured metabolite levels derived from injected [1-13 C]glucose and [1,2-13 C]acetate (i.p.) in cerebral cortex and spinal cord extracts of wild type and hSOD1G93A mice at onset and mid disease stages using high-pressure liquid chromatography,1 H and13 C nuclear magnetic resonance spectroscopy. Levels of spinal and cortical CNS total lactate, [3-13 C]lactate, total alanine and [3-13 C]alanine, but not cortical glucose and [1-13 C]glucose, were reduced mostly at mid stage indicating impaired glycolysis...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Gang Xiao, Lai N Chan, Lars Klemm, Daniel Braas, Zhengshan Chen, Huimin Geng, Qiuyi Chen Zhang, Ali Aghajanirefah, Kadriye Nehir Cosgun, Teresa Sadras, Jaewoong Lee, Tamara Mirzapoiazova, Ravi Salgia, Thomas Ernst, Andreas Hochhaus, Hassan Jumaa, Xiaoyan Jiang, David M Weinstock, Thomas G Graeber, Markus Müschen
B cell activation during normal immune responses and oncogenic transformation impose increased metabolic demands on B cells and their ability to retain redox homeostasis. While the serine/threonine-protein phosphatase 2A (PP2A) was identified as a tumor suppressor in multiple types of cancer, our genetic studies revealed an essential role of PP2A in B cell tumors. Thereby, PP2A redirects glucose carbon utilization from glycolysis to the pentose phosphate pathway (PPP) to salvage oxidative stress. This unique vulnerability reflects constitutively low PPP activity in B cells and transcriptional repression of G6PD and other key PPP enzymes by the B cell transcription factors PAX5 and IKZF1...
March 6, 2018: Cell
Diana Fang, Eduardo N Maldonado
Cancer metabolism is emerging as a chemotherapeutic target. Enhanced glycolysis and suppression of mitochondrial metabolism characterize the Warburg phenotype in cancer cells. The flux of respiratory substrates, ADP, and Pi into mitochondria and the release of mitochondrial ATP to the cytosol occur through voltage-dependent anion channels (VDACs) located in the mitochondrial outer membrane. Catabolism of respiratory substrates in the Krebs cycle generates NADH and FADH2 that enter the electron transport chain (ETC) to generate a proton motive force that maintains mitochondrial membrane potential (ΔΨ) and is utilized to generate ATP...
2018: Advances in Cancer Research
Dina Vojinovic, Sven J van der Lee, Cornelia M van Duijn, Meike W Vernooij, Maryam Kavousi, Najaf Amin, Ayşe Demirkan, M Arfan Ikram, Aad van der Lugt, Daniel Bos
BACKGROUND AND AIMS: Increasing evidence shows that intracranial carotid artery atherosclerosis may develop under the influence of a differential metabolic risk factor profile than atherosclerosis in the extracranial part of the carotid artery. To further elucidate these differences, we investigated associations of a wide range of circulating metabolites with intracranial and extracranial carotid artery atherosclerosis. METHODS: From the population-based Rotterdam Study, blood samples from 1111 participants were used to determine a wide range of metabolites by proton nuclear magnetic resonance (NMR)...
March 8, 2018: Atherosclerosis
Gosse Overal, Bas Teusink, Frank J Bruggeman, Josephus Hulshof, Robert Planqué
Yeast glycolysis has been the focus of research for decades, yet a number of dynamical aspects of yeast glycolysis remain poorly understood at present. If nutrients are scarce, yeast will provide its catabolic and energetic needs with other pathways, but the enzymes catalysing upper glycolytic fluxes are still expressed. We conjecture that this overexpression facilitates the rapid transition to glycolysis in case of a sudden increase in nutrient concentration. However, if starved yeast is presented with abundant glucose, it can enter into an imbalanced state where glycolytic intermediates keep accumulating, leading to arrested growth and cell death...
March 14, 2018: Mathematical Biosciences
X Dong, Z Zhou, L Wang, B Saremi, A Helmbrecht, Z Wang, J J Loor
Amino acids not only serve as precursors for protein synthesis but also function as signaling molecules that can regulate the mammalian target of rapamycin (mTOR) pathway. Methionine and Lys are the most-limiting AA for milk production and a ratio of ∼3:1 Lys:Met in the metabolizable protein has been determined to be ideal. Besides Met and Lys, recent studies have evaluated Ile, Leu, Val, and Thr as potentially limiting for milk protein synthesis. The objective of this experiment was to determine if varying the ratio of Lys:Thr, Lys:Ile, Lys:Val, and Lys:Leu while maintaining an ideal ratio of Lys:Met and fixed ratio of other essential AA (IPAA) elicits changes in intracellular metabolites, gene transcription related to protein synthesis, and phosphorylation status of mTOR pathway proteins...
March 14, 2018: Journal of Dairy Science
B Fang, M Zhang, K S Ge, H Z Xing, F Z Ren
Previous studies have demonstrated that the anti-tumor α-lactalbumin-oleic acid complex (α-LA-OA) may target the glycolysis of tumor cells. However, few data are available regarding the effects of α-LA-OA on energy metabolism. In this study, we measured glycolysis and mitochondrial functions in HeLa cells in response to α-LA-OA using the XF flux analyzer (Seahorse Bioscience, North Billerica, MA). The gene expression of enzymes involved in glycolysis, tricarboxylic acid cycle, electron transfer chain, and ATP synthesis were also evaluated...
March 14, 2018: Journal of Dairy Science
Baomei Wu, Li Li, Tianhang Qiu, Xi Zhang, Suxia Cui
Rice cytoplasmic APX2 is a pleiotropic protein, densely distributed around chloroplasts. It plays key roles in H2 O2 homeostasis and chloroplast protection, and is related to plant architecture and fertility regulation. Ascorbate peroxidases (APXs) catalyze the conversion of H2 O2 into H2 O. In this report, we systematically investigated the function of cytosolic APX2 using a T-DNA knockout mutant. Loss of OsAPX2 altered rice architecture including shoot height and leaf inclination, resulting in shoot dwarfing, leaf dispersion and fertility decline...
March 16, 2018: Plant Cell Reports
Kalimuthusamy Natarajaseenivasan, Bianca Cotto, Santhanam Shanmughapriya, Alyssa A Lombardi, Prasun K Datta, Muniswamy Madesh, John W Elrod, Kamel Khalili, Dianne Langford
Calcium (Ca2+ ) dynamics and oxidative signaling control mitochondrial bioenergetics in the central nervous system, where astrocytes are a major energy source for neurons. Cocaine use exacerbates HIV-associated neurocognitive disorders, but little is known about disruptions in astrocyte metabolism in this context. Our data show that the HIV protein Tat and cocaine induce a metabolic switch from glucose to fatty acid oxidation in astrocytes, thereby limiting lactate transport to neurons. Mechanistic analyses revealed increased Mitochondrial Ca2+ Uniporter (MCU)-mediated Ca2+ uptake in astrocytes exposed to Tat and cocaine due to oxidation of MCU...
March 16, 2018: Cell Death & Disease
Maria Eugenia Sabatino, Ezequiel Grondona, Liliana D V Sosa, Bethania Mongi Bragato, Lucia Carreño, Virginia Juarez, Rodrigo A da Silva, Aline Remor, Lucila de Bortoli, Roberta de Paula Martins, Pablo A Pérez, Juan Pablo Petiti, Silvina Gutiérrez, Alicia I Torres, Alexandra Latini, Ana L De Paul
The cellular transformation of normal functional cells to neoplastic ones implies alterations in the cellular metabolism and mitochondrial function in order to provide the bioenergetics and growth requirements for tumour growth progression. Currently, the mitochondrial physiology and dynamic shift during pituitary tumour development are not well understood. Pituitary tumors present endocrine neoplastic benign growth which, in previous reports, we had shown that in addition to increased proliferation, these tumours were also characterized by cellular senescence signs with no indication of apoptosis...
March 13, 2018: Free Radical Biology & Medicine
Yong-Il Kim, Jin Chul Paeng, Young Sik Park, Gi Jeong Cheon, Dong Soo Lee, June-Key Chung, Keon Wook Kang
OBJECTIVE: The purposes of this study were to assess the relation between epidermal growth factor receptor (EGFR) mutation status and FDG PET/CT findings and to evaluate the influence of this relation on the use of FDG PET/CT parameters to establish a prognosis in cases of localized lung adenocarcinoma. MATERIALS AND METHODS: Patients with stage I and II lung adenocarcinomas were retrospectively enrolled. At the initial FDG PET/CT examination, maximum and peak standardized uptake, tumor-to-background ratio, and volumetric parameters of metabolic tumor volume and total lesion glycolysis were measured...
March 16, 2018: AJR. American Journal of Roentgenology
Jilong Zhou, Chengyu Li, Wang Yao, Alsiddig M A, Lijun Huo, Honglin Liu, Yi-Liang Miao
Autophagy is an essential cellular mechanism that degrades cytoplasmic proteins and organelles to recycle their components. Here we showed that autophagy was essential for the glycolysis switch and energy homeostasis in mouse granulosa cells (MGCs) under hypoxic condition. Our data indicated that hypoxia inducible factor-1α (HIF-1α) could be largely increased in developing follicles and this remarkable upregulation of HIF-1α triggered cell autophagy and glucose uptake. We found that blocking autophagy by Atg7 knockdown and 3-methyladenine (3-MA) treatment affected the glucose metabolism, with increased glycolytic enzyme activity and decreased ATP production...
March 13, 2018: Biology of Reproduction
Fariba Tayyari, G A Nagana Gowda, Olufunmilayo F Olopade, Richard Berg, Howard H Yang, Maxwell P Lee, Wilfred F Ngwa, Suresh K Mittal, Daniel Raftery, Sulma I Mohammed
Breast cancer, a heterogeneous disease with variable pathophysiology and biology, is classified into four major subtypes. While hormonal- and antibody-targeted therapies are effective in the patients with luminal and HER-2 subtypes, the patients with triple-negative breast cancer (TNBC) subtype do not benefit from these therapies. The incidence rates of TNBC subtype are higher in African-American women, and the evidence indicates that these women have worse prognosis compared to women of European descent. The reasons for this disparity remain unclear but are often attributed to TNBC biology...
February 20, 2018: Oncotarget
Krishna B Singh, Eun-Ryeong Hahm, Lora H Rigatti, Daniel P Normolle, Jian-Min Yuan, Shivendra V Singh
We have shown previously that dietary administration of phenethyl isothiocyanate (PEITC), a small molecule from edible cruciferous vegetables, significantly decreases the incidence of poorly-differentiated prostate cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice without any side effects. In this study, we investigated the role of c-Myc-regulated glycolysis in prostate cancer chemoprevention by PEITC. Exposure of LNCaP (androgen-responsive) and 22Rv1 (castration-resistant) human prostate cancer cells to PEITC resulted in suppression of expression as well as transcriptional activity of c-Myc...
March 15, 2018: Cancer Prevention Research
Jun-Ho Cho, Goo-Young Kim, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), a key enzyme in endogenous glucose production. This autosomal recessive disorder is characterized by impaired glucose homeostasis and long-term complications of hepatocellular adenoma/carcinoma (HCA/HCC). We have shown that hepatic G6Pase-α deficiency-mediated steatosis leads to defective autophagy that is frequently associated with carcinogenesis. We now show that hepatic G6Pase-α deficiency also leads to enhancement of hepatic glycolysis and hexose monophosphate shunt (HMS) that can contribute to hepatocarcinogenesis...
March 12, 2018: Biochemical and Biophysical Research Communications
Mohammad Golam Mostofa, Ajit Ghosh, Zhong-Guang Li, Md Nurealam Siddiqui, Masayuki Fujita, Lam-Son Phan Tran
Abiotic stresses are the most common harmful factors, adversely affecting all aspects of plants' life. Plants have to elicit appropriate responses against multifaceted effects of abiotic stresses by reprogramming various cellular processes. Signaling molecules play vital roles in sensing environmental stimuli to modulate gene expression, metabolism and physiological processes in plants to cope with the adverse effects. Methylglyoxal (MG), a dicarbonyl compound, is known to accumulate in cells as a byproduct of various metabolic pathways, including glycolysis...
March 12, 2018: Free Radical Biology & Medicine
Stefanie Amend, Roland Frankenberger, Susanne Lücker, Eugen Domann, Norbert Krämer
OBJECTIVES: The present study aimed to establish Lactobacillus casei in a completely automated Streptococcus mutans-based artificial mouth model and to investigate secondary caries inhibiting properties of glass ionomer cements / resin composite groups in vitro. METHODS: Sixty extracted, caries-free human third molars were used for preparation of standardized class-V-cavities. Specimens were restored with a resin-modified (Photac Fil; PF) as well as a conventional glass ionomer cement (Ketac Molar; KM) and one resin composite bonded with and without conduction of etch-and-rinse technique (Prime&Bond NT, Ceram X mono; C+ERT, C)...
March 12, 2018: Dental Materials: Official Publication of the Academy of Dental Materials
David B Medeiros, Leonardo Perez de Souza, Werner C Antunes, Wagner L Araújo, Danilo M Daloso, Alisdair R Fernie
Sucrose has long been thought to play an osmolytic role in stomatal opening. However, recent evidence supports the idea that the role of sucrose in this process is primarily energetic. Here we used a combination of stomatal aperture assays coupled with kinetic [U-13 C]-sucrose isotope labelling experiments to confirm that sucrose is degraded during light-induced stomatal opening and to define the fate of the C released from sucrose breakdown. We additionally show that addition of sucrose in the medium did not enhance light-induced stomatal opening...
March 15, 2018: Plant Journal: for Cell and Molecular Biology
Shuping Yang, Xin Li, Xinfeng Liu, Xiangbin Ding, Xiangbo Xin, Congfei Jin, Sheng Zhang, Guangpeng Li, Hong Guo
MSTN -encoded myostatin is a negative regulator of skeletal muscle development. Here, we utilized the gluteus tissues from MSTN gene editing and wild type Luxi beef cattle which are native breed of cattle in China, performed tandem mass tag (TMT) -based comparative proteomics and phosphoproteomics analyses to investigate the regulatory mechanism of MSTN related to cellular metabolism and signaling pathway in muscle development. Out of 1,315 proteins, 69 differentially expressed proteins (DEPs) were found in global proteomics analysis...
February 16, 2018: Oncotarget
Jian Lu, Min Chen, Sumeng Gao, Jigang Yuan, Zhu Zhu, Xiaoping Zou
The 'Warburg effect' is considered a vital hallmark of cancer cells, characterized by an altered metabolism, in which cells rely on aerobic glycolysis. As a key enzyme of aerobic glycolysis, pyruvate kinase M2 (PKM2) serves a crucial role in tumorigenesis. Accumulating studies have indicated that PKM2 is a potential target for cancer therapy. The aim of the present study was to assess the anticancer effects of LY294002, a specific phosphatidylinositol-3-kinase inhibitor, on gastric cancer (GC) cells and further explore its possible mechanism in vitro ...
April 2018: Oncology Letters
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