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metabolism reprogramming

Mikhail Ryzhikov, Anna Ehlers, Deborah Steinberg, Wenfang Xie, Eitan Oberlander, Samuel Brown, Petra E Gilmore, Reid R Townsend, William S Lane, Tamas Dolinay, Kiichi Nakahira, Augustine M K Choi, Jeffrey A Haspel
Circadian rhythms are a hallmark of physiology, but how such daily rhythms organize cellular catabolism is poorly understood. Here, we used proteomics to map daily oscillations in autophagic flux in mouse liver and related these rhythms to proteasome activity. We also explored how systemic inflammation affects the temporal structure of autophagy. Our data identified a globally harmonized rhythm for basal macroautophagy, chaperone-mediated autophagy, and proteasomal activity, which concentrates liver proteolysis during the daytime...
February 12, 2019: Cell Reports
Uwe Druege, Alexander Hilo, José Manuel Pérez-Pérez, Yvonne Klopotek, Manuel Acosta, Fahimeh Shahinnia, Siegfried Zerche, Philipp Franken, Mohammad R Hajirezaei
Background: Adventitious root (AR) formation in excised plant parts is a bottleneck for survival of isolated plant fragments. AR formation plays an important ecological role and is a critical process in cuttings for the clonal propagation of horticultural and forestry crops. Therefore, understanding the regulation of excision-induced AR formation is essential for sustainable and efficient utilization of plant genetic resources. Scope: Recent studies of plant transcriptomes, proteomes and metabolomes, and the use of mutants and transgenic lines have significantly expanded our knowledge concerning excision-induced AR formation...
February 11, 2019: Annals of Botany
Huabo Wang, Jie Lu, Sucheta Kulkarni, Weiqi Zhang, Joanna E Gorka, Jordan A Mandel, Eric S Goetzman, Edward V Prochownik
Eukaryotic cell metabolism consists of processes that generate available energy, such as glycolysis, the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) and those that consume it, including macromolecular synthesis, the maintenance of ionic gradients and cellular detoxification. By converting pyruvate to acetyl-CoA (AcCoA), the pyruvate dehydrogenase (PDH) complex (PDC) links glycolysis and the TCA cycle. Surprisingly, disrupting the connection between glycolysis and the TCA cycle by inactivation PDC has only minor effects on cell replication...
February 12, 2019: Journal of Biological Chemistry
Nathan Clendenen, Geoffrey R Nunns, Ernest E Moore, Eduardo Gonzalez, Michael Chapman, Julie A Reisz, Erik Peltz, Miguel Fragoso, Travis Nemkov, Matthew J Wither, Angela Sauaia, Christopher C Silliman, Kirk Hansen, Anirban Banerjee, Angelo D'alessandro, Hunter B Moore
BACKGROUND: Understanding the molecular mechanisms in perturbation of the metabolome following ischaemia and reperfusion is critical in developing novel therapeutic strategies to prevent the sequelae of post-injury shock. While the metabolic substrates fueling these alterations have been defined, the relative contribution of specific organs to the systemic metabolic reprogramming secondary to ischaemic or haemorrhagic hypoxia remains unclear. MATERIALS AND METHODS: A porcine model of selected organ ischaemia was employed to investigate the relative contribution of liver, kidney, spleen and small bowel ischaemia/reperfusion to the plasma metabolic phenotype, as gleaned through ultra-high performance liquid chromatography-mass spectrometry-based metabolomics...
December 13, 2018: Blood Transfusion, Trasfusione del Sangue
Rakshamani Tripathi, Zulong Liu, Rina Plattner
Purpose of Review: The goal of this review is to summarize our current knowledge regarding how ABL family kinases are activated in solid tumors and impact on solid tumor development/progression, with a focus on recent advances in the field. Recent Findings: Although ABL kinases are known drivers of human leukemia, emerging data also implicates the kinases in a large number of solid tumor types where they promote diverse processes such as proliferation, survival, cytoskeletal reorganization, cellular polarity, EMT (epithelial-mesenchymal-transition), metabolic reprogramming, migration, invasion and metastasis via unique signaling pathways...
October 2018: Current Pharmacology Reports
Jun Zhang, Lin Jia, Tengfei Liu, Yim Ling Yip, Wing Chung Tang, Weitao Lin, Wen Deng, Kwok Wai Lo, Chanping You, Maria Li Lung, Hong Lok Lung, Annie Lai-Man Cheung, Sai Wah Tsao, Chi Man Tsang
EBV infection of preinvasive nasopharyngeal epithelium is believed to be an initiation step during pathogenesis of nasopharyngeal carcinoma (NPC), but the mechanisms remain poorly understood. Here we report a novel mechanism driving NPC metastasis through the EBV-encoded LMP1-mediated metabolic reprogramming, via activation of IGF1-mTORC2 signaling and nuclear acetylation of the Snail promoter by the PDHE1α, an enzyme involved in glucose metabolism. Mechanistically, EBV-LMP1 increases the cellular secretion of IGF1 which promotes phosphorylation of IGF1R to activate mTORC2/AKT signaling linking glucose metabolism to cell motility...
February 11, 2019: Oncogene
Ines Ugele, Zugey Elizabeth Cárdenas-Conejo, Kathrin Hammon, Monika Wehrstein, Christina Bruss, Katrin Peter, Katrin Singer, Eva Gottfried, Jakob Boesch, Peter Oefner, Katja Dettmer, Kathrin Renner, Marina Kreutz
Mutations in isocitrate dehydrogenase (IDH) or a reduced expression of L-2-hydroxyglutarate (HG)-dehydrogenase result in accumulation of D-2-HG or L-2-HG, respectively, in tumor tissues. D-2-HG and L-2-HG have been shown to affect T-cell differentiation and activation; however, effects on human myeloid cells have not been investigated so far. In this study we analyzed the impact of D-2-HG and L-2-HG on activation and maturation of human monocyte-derived dendritic cells (DCs). 2-HG was taken up by DCs and had no impact on cell viability but diminished CD83 expression after Lipopolysaccharides (LPS) stimulation...
February 10, 2019: International Journal of Molecular Sciences
Andres Ainelo, Rando Porosk, Kalle Kilk, Sirli Rosendahl, Jaanus Remme, Rita Hõrak
The potentially self-poisonous toxin-antitoxin modules are widespread in bacterial chromosomes, but despite extensive studies, their biological importance remains poorly understood. Here, we used whole-cell proteomics to study the cellular effects of the Pseudomonas putida toxin GraT that is known to inhibit growth and ribosome maturation in a cold-dependent manner when the graA antitoxin gene is deleted from the genome. Proteomic analysis of P. putida wild-type and Δ graA strains at 30 °C and 25 °C, where the growth is differently affected by GraT, revealed two major responses to GraT at both temperatures...
February 9, 2019: Toxins
Martin A Prusinkiewicz, Joe S Mymryk
Viruses are obligate intracellular parasites that alter many cellular processes to create an environment optimal for viral replication. Reprogramming of cellular metabolism is an important, yet underappreciated feature of many viral infections, as this ensures that the energy and substrates required for viral replication are available in abundance. Human adenovirus (HAdV), which is the focus of this review, is a small DNA tumor virus that reprograms cellular metabolism in a variety of ways. It is well known that HAdV infection increases glucose uptake and fermentation to lactate in a manner resembling the Warburg effect observed in many cancer cells...
February 8, 2019: Viruses
Chong Chen, Lipeng Bai, Fengqi Cao, Shengnan Wang, Huiwen He, Mingcheng Song, Huilin Chen, Yan Liu, Jian Guo, Qin Si, Yundi Pan, Ruizhe Zhu, Tsung-Hsien Chuang, Rong Xiang, Yunping Luo
The altered metabolism and acidic microenvironment plays an important role in promoting tumor malignant characteristics. A small population of cancer stem cells (CSCs) were considered as a therapy target to reserve tumor relapse, resistance, and metastasis. However, the molecular mechanism that regulates CSCs metabolism remains poorly understood. In this study, we demonstrate a fundamental role of stemness gene LIN28B in maintaining CSCs glycolysis metabolism. Using LIN28B-expressing cancer cell lines, we found that the rate of extracellular acidification, glucose uptake, and lactate secretion are all suppressed by LIN28B knockdown in vitro and in vivo...
February 11, 2019: Oncogene
Bin Liu, Wenjie Bai, Guoyao Ou, Jun Zhang
Cdh1 is a regulatory subunit of the anaphase promoting complex/cyclosome (APC/C), known to be involved in regulating neuronal survival. The role of Cdh1 in volatile anesthetics-induced neuronal apoptosis in the developing brain is unknown. In this study, we used postnatal day 7 (P7) and day 21 (P21) mice exposed to 2.3% sevoflurane for 6 h to investigate at which age and duration of exposure sevoflurane affects the expression of Cdh1 and glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and that of the pentose phosphate pathway (PPP) enzyme, Glucose-6-phosphate dehydrogenase (G6PD)...
February 11, 2019: ACS Chemical Neuroscience
Mehri Bemani Naeini, Amir Abbas Momtazi, Mahmoud Reza Jaafari, Thomas P Johnston, George Barreto, Maciej Banach, Amirhossein Sahebkar
Lipid metabolism plays an important role in cancer development due to the necessities of rapidly dividing cells to increase structural, energetic, and biosynthetic demands for cell proliferation. Basically, obesity, type 2 diabetes, and other related diseases, and cancer are associated with a common hyperactivated "lipogenic state." Recent evidence suggests that metabolic reprogramming and overproduction of enzymes involved in the synthesis of fatty acids are the new hallmarks of cancer, which occur in an early phase of tumorigenesis...
February 11, 2019: Journal of Cellular Physiology
Francesca Sciarretta, Chiara Fulci, Camilla Palumbo, Katia Aquilano, Anna Pastore, Egidio Iorio, Daniele Lettieri-Barbato, Rosella Cicconi, Antonella Minutolo, Mariacristina Parravano, Marta Gilardi, Monica Varano, Anna Maria Caccuri
Glutathione transferases (GSTs) play an important role in retinal pathophysiology. Within this family, the GSTP isoform is known as an endogenous regulator of cell survival and proliferation pathways and of cellular responses to oxidative stress. In the present study we silenced GSTP in R28 cells, a retinal precursor cell line with markers of both glial and neuronal origin, and obtained stable clones which were viable and, unexpectedly, characterized by a more neuronal phenotype. The degree of neuronal differentiation was inversely correlated with GSTP residual expression levels...
February 11, 2019: Journal of Cellular Physiology
Xiaojing Huo, Hankun Li, Zhen Li, Chuan Yan, Sinnakaruppan Mathavan, Jianjun Liu, Zhiyuan Gong
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is mainly due to genetic changes in hepatocytes. However, molecular expression in hepatocytes during hepatocarcinogenesis has not been characterized. In this study, using an inducible kras transgenic zebrafish models for HCC, transcriptomic profiles of oncogenic hepatocytes from larvae, male and female adult fish following a brief induction of oncogenic kras were investigated. We found that oncogenic hepatocytes from all the three sources possess most of the cancer hallmarks at molecular level, including Sustaining proliferative signaling, Evading growth suppressors, Resisting cell death, Avoiding immune destruction, Inflammation, Reprogramming of energy metabolism, Angiogenesis, and Activating invasion and metastasis, suggesting the malignant transformation at molecular level could occur at the early stage of hepatocarcinogensis and can be captured in hepatocytes...
February 7, 2019: Biochemical and Biophysical Research Communications
Hongfei Qiao, Xijing He, Qiaojun Zhang, Haifeng Yuan, Dong Wang, Libo Li, Yanping Hui, Zhonghen Wu, Wenjuan Li, Ni Zhang
After spinal cord injury, microglial cells are activated and converted to an M1 phenotype. Emerging evidence supports the hypothesis that glucose reprogramming accompanies microglial activation. What contributes to the activation of microglia and glucose reprogramming, however, remains unclear. In the current study, we investigated the role and underlying mechanism of a-synuclein in regulating the aerobic glycolysis in microglia. We found that a-synuclein contributed to the reprogramming of glucose metabolism in microglia by promoting glycolysis and inhibiting mitochondrial biogenesis and oxidative phosphorylation...
February 6, 2019: International Journal of Biological Macromolecules
Bok Sil Hong, Han Suk Ryu, Namshin Kim, Jisun Kim, Eunshin Lee, Hyunhye Moon, Kyoung Hyoun Kim, Min-Sun Jin, Nam Hoon Kwon, Sunghoon Kim, Donghyun Kim, Doo Hyun Chung, Kyeonghun Jeong, Kwangsoo Kim, Ki Yoon Kim, Han-Byoel Lee, Wonshik Han, Jihui Yun, Jong-Il Kim, Dong-Young Noh, Hyeong-Gon Moon
Various microRNAs (miRNAs) play critical roles in the development and progression of solid tumors. In this study, we describe the role of miR-204-5p in limiting growth and progression of breast cancer. In breast cancer tissues, miR-204-5p was significantly downregulated compared to normal breast tissues, and its expression levels were associated with increased survival outcome in breast cancer patients. Overexpression of miR-204-5p inhibited viability, proliferation, and migration capacity in human and murine breast cancer cells...
February 8, 2019: Cancer Research
Huan Liu, Monireh Marsafari, Li Deng, Peng Xu
Lipogenesis is a complicated process involving global transcriptional reprogramming of lipogenic pathways. It is commonly believed that nitrogen starvation triggers a metabolic shift that reroutes carbon flux from Krebs cycles to lipogenesis. In this study, we systematically surveyed and dynamically profiled the transcriptional activity of 22 lipogenic promoters aiming to delineate a picture how nitrogen starvation regulates lipogenesis in Y. lipolytica. These lipogenic promoters drive the expression of critical pathways that are responsible for the generation of reducing equivalents (NADPH), carbon backbones (acetyl-CoA, malonyl-CoA, DHAP, etc...
February 7, 2019: Applied Microbiology and Biotechnology
Shibdas Banerjee, Soumen Kanti Manna
Metabolic reprogramming is a hallmark of tumor development. A technique that can map this complex biochemical shift by taking a snapshot of various metabolites in a tissue specimen (biopsy) is of high utility in the context of cancer diagnosis. Desorption electrospray ionization mass spectrometric imaging (DESI-MSI) is such a powerful and emerging analytical technique to simultaneously visualize the distributions of hundreds of metabolites, lipids, and other small molecules in the biological tissue. In DESI-MSI, a fine spray of high-velocity charged microdroplets rapidly extracts molecular species from the tissue surface and subsequently transfers them to the mass spectrometer, while the sample is continuously moved in two dimensions under the impinging spray of microdroplets...
2019: Methods in Molecular Biology
Tanushree Chakraborty, Soumen Kanti Manna
Cancer poses a daunting challenge to researchers and clinicians alike. Early diagnosis, accurate prognosis, and prediction of therapeutic response remain elusive in most types of cancer. In addition, lacunae in our understanding of cancer biology continue to hinder advancement of therapeutic strategies. Metabolic reprogramming has been identified as integral to pathogenesis and progression of the disease. Consequently, analysis of biofluid metabolome has emerged as a promising approach to further our understanding of disease biology as well as to identify cancer biomarkers...
2019: Methods in Molecular Biology
David Kung-Chun Chiu, Misty Shuo Zhang, Aki Pui-Wah Tse, Carmen Chak-Lui Wong
Blood vessels in tumors contain chaotic branching structures and leaky vessel lumens, resulting in uneven supply of oxygen in the tumor microenvironment. High metabolic and proliferation rate of tumor cells further depletes the local oxygen supply. Therefore, hypoxia is a common phenomenon in multiple solid malignancies. Hypoxia-inducible factors (HIFs) regulate the transcription of a spectrum of genes, which are vitally important for tumor cell adaption under hypoxia, and shape the tumor microenvironment to become more favorable for progression...
2019: Methods in Molecular Biology
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