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Cells Signaling Nutrients

Qi Shen, Jie Wang, Chen-Xi Liu, Wei Cui, Lei Zhang, Yu-Chao Zhang, Yue Wang, Jing Wu, Jian-Xin Li
Pancreatic cancer is one of the most deadly neoplasm with a 5-year survival rate of less than 6% owing to its remarkable tolerance to nutrient starvation, and new drugs and treatment strategies are urgently needed. During a project aiming at discovery of anticancer agents, we performed a structure modification on polycyclic polyprenylated acylphloroglucinols (PPAPs) skeleton, and discovered that PPAP rearranged to a tetrahydroquinolin-2(1H)-one feature. Here, series of tetrahydroquinolin-2(1H)-one derivatives were designed, synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (PANC-1), and the structure-activity relationship was also discussed...
March 9, 2019: European Journal of Medicinal Chemistry
Vladimir Beljanski, Karl-Henrik Grinnemo, Cecilia Österholm
Stem cells (SCs) have been proven to possess regenerative and immunomodulatory properties and can be used to treat diseases that involve loss of cells due to tissue damage or inflammation. For this approach to succeed, SCs or their derivatives should be able to engraft in the target tissue at least for a short period of time. Unfortunately, once injected, therapeutic SCs will encounter a hostile environment, including hypoxia, lack of nutrients and stromal support, and cells may also be targeted and rejected by the immune system...
March 12, 2019: Cytotherapy
Alessandro Zannini, Alessandra Rustighi, Elena Campaner, Giannino Del Sal
Cellular choices are determined by developmental and environmental stimuli through integrated signal transduction pathways. These critically depend on attainment of proper activation levels that in turn rely on post-translational modifications (PTMs) of single pathway members. Among these PTMs, post-phosphorylation prolyl-isomerization mediated by PIN1 represents a unique mechanism of spatial, temporal and quantitative control of signal transduction. Indeed PIN1 was shown to be crucial for determining activation levels of several pathways and biological outcomes downstream to a plethora of stimuli...
2019: Frontiers in Oncology
Pranvera Sadiku, Sarah R Walmsley
Inflamed and infected tissue sites are characterised by oxygen and nutrient deprivation. The cellular adaptations to insufficient oxygenation, hypoxia, are mainly regulated by a family of transcription factors known as hypoxia-inducible factors (HIFs). The protein members of the HIF signalling pathway are critical regulators of both the innate and adaptive immune responses, and there is an increasing body of evidence to suggest that the elicited changes occur through cellular metabolic reprogramming. Here, we review the literature on innate immunometabolism to date and discuss the role of hypoxia in innate cell metabolic reprogramming, and how this determines immune responses...
March 14, 2019: EMBO Reports
Miriam Piles, Carlos Fernandez-Lozano, María Velasco-Galilea, Olga González-Rodríguez, Juan Pablo Sánchez, David Torrallardona, Maria Ballester, Raquel Quintanilla
BACKGROUND: To date, the molecular mechanisms that underlie residual feed intake (RFI) in pigs are unknown. Results from different genome-wide association studies and gene expression analyses are not always consistent. The aim of this research was to use machine learning to identify genes associated with feed efficiency (FE) using transcriptomic (RNA-Seq) data from pigs that are phenotypically extreme for RFI. METHODS: RFI was computed by considering within-sex regression on mean metabolic body weight, average daily gain, and average backfat gain...
March 13, 2019: Genetics, Selection, Evolution: GSE
Xiaofeng Li, Wengui Xu
Impaired antitumor immunity or induced immunosuppression in the tumor microenvironment contributes significantly to tumor progression and resistance to immunotherapy. It is becoming increasingly recognized that dynamic metabolic programming orchestrates appropriate immune responses, whereas incorrect metabolic reprogramming may underlie aberrant immune remodeling. Furthermore, pathways that control cellular metabolism and immune cell function by transcriptional and post‑transcriptional mechanisms are intimately interlinked, including hypo-xia‑inducible factor 1α, c‑Myc and phosphatidylinositol 3‑kinase/protein kinase B/mammalian target of rapamycin signaling...
March 4, 2019: Oncology Reports
Hao Yang, Rongxuan Zhu, Xiaoping Zhao, Liu Liu, Zhaoli Zhou, Li Zhao, Beibei Liang, Wenjing Ma, Jian Zhao, Jianjun Liu, Gang Huang
Tumor cells undergo a metabolic shift in order to adapt to the altered microenvironment, although the underlying mechanisms have not been fully explored. HnRNP A1 is involved in the alternative splicing of the pyruvate kinase (PK) mRNA, allowing tumor cells to specifically produce the PKM2 isoform. We found that the acetylation status of hnRNP A1 in hepatocellular carcinoma (HCC) cells was dependent on glucose availability, which affected the PKM2-dependent glycolytic pathway. In the glucose-starved HCC cells, SIRT1 and SIRT6, members of deacetylase sirtuin family, were highly expressed and deacetylated hnRNP A1 after direct binding...
March 11, 2019: Oncogene
Elizabeth M Hart, Aileen O'Connell, Kimberly Tang, Joseph S Wzorek, Marcin Grabowicz, Daniel Kahne, Thomas J Silhavy
The Gram-negative outer membrane (OM) is a selectively permeable asymmetric bilayer that allows vital nutrients to diffuse into the cell but prevents toxins and hydrophobic molecules from entering. Functionally and structurally diverse β-barrel outer membrane proteins (OMPs) build and maintain the permeability barrier, making the assembly of OMPs crucial for cell viability. In this work, we characterize an assembly-defective mutant of the maltoporin LamB, lamBG439D We show that the folding defect of LamBG439D results in an accumulation of unfolded substrate that is toxic to the cell when the periplasmic protease DegP is removed...
March 11, 2019: Journal of Bacteriology
Kok-Lun Pang, Kok-Yong Chin
Obesity is a major risk factor for diabetes, and these two metabolic conditions cause significant healthcare burden worldwide. Chronic inflammation and increased oxidative stress due to exposure of cells to excess nutrients in obesity may trigger insulin resistance and pancreatic β-cell dysfunction. Tocotrienol, as a functional food component with anti-inflammatory, antioxidant, and cell signaling-mediating effects, may be a potential agent to complement the current management of obesity and diabetes. The review aimed to summarize the current evidence on the anti-obesity and antidiabetic effects of tocotrienol...
March 6, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Nathan J Holmes, Herbert W Kavunja, Yong Yang, B Dillon Vannest, Claudia N Ramsey, Dana M Gepford, Nicholas Banahene, Anne W Poston, Brent F Piligian, Donald R Ronning, Anil K Ojha, Benjamin M Swarts
The mycobacterial outer membrane, or mycomembrane, is essential for the viability and virulence of Mycobacterium tuberculosis and related pathogens. The mycomembrane is a dynamic structure, whose chemical composition and biophysical properties can change during stress to give an advantage to the bacterium. However, the mechanisms that govern mycomembrane remodeling and their significance to mycobacterial pathogenesis are still not well characterized. Recent studies have shown that trehalose dimycolate (TDM), a major glycolipid of the mycomembrane, is broken down by the mycobacteria-specific enzyme TDM hydrolase (Tdmh) in response to nutrient deprivation, a process which appears to modulate the mycomembrane to increase nutrient acquisition, but at the expense of stress tolerance...
February 28, 2019: ACS Omega
Jacky Chow, Heather M Dionne, Aditi Prabhakar, Amit Mehrotra, Jenn Somboonthum, Beatriz Gonzalez, Mira Edgerton, Paul J Cullen
Many fungal species, including pathogens, undergo a morphogenetic response called filamentous growth, where cells differentiate into a specialized cell type to promote nutrient foraging and surface colonization. Despite the fact that filamentous growth is required for virulence in some plant and animal pathogens, certain aspects of this behavior remain poorly understood. By examining filamentous growth in the budding yeast Saccharomyces cerevisiae and the opportunistic pathogen Candida albicans , we identify responses where cells undergo filamentous growth in groups of cells or aggregates...
March 6, 2019: MSphere
Gemma Sangüesa, Núria Roglans, Miguel Baena, Ana Magdalena Velázquez, Juan Carlos Laguna, Marta Alegret
One of the most important threats to global human health is the increasing incidences of metabolic pathologies (including obesity, type 2 diabetes and non-alcoholic fatty liver disease), which is paralleled by increasing consumptions of hypercaloric diets enriched in simple sugars. The challenge is to identify the metabolic pathways affected by the excessive consumption of these dietary components when they are consumed in excess, to unravel the molecular mechanisms leading to metabolic pathologies and identify novel therapeutic targets to manage them...
March 5, 2019: International Journal of Molecular Sciences
Zuo Rui, Wang Yanqiu, Li Jie, Wu Junlong, Wang Wenkai, Li Bin, Sun Chao, Wang Ziwen, Shi Chunmeng, Yue Zhou, Liu Minghan, Zhang Chao
Cartilage endplate (CEP) calcification inhibits the transport of metabolites and nutrients in the intervertebral disc and is an important initiating factor of intervertebral disc degeneration (IDD). However, the mechanisms governing CEP degeneration have not been thoroughly elucidated. In this study, we established a mouse CEP degeneration model and showed that autophagy insufficiency caused the degeneration of CEP. We found that the inflammatory cytokine tumor necrosis factor alpha (TNF-α) increased the level of intracellular reactive oxygen species (ROS) and caused cell senescence and osteogenic differentiation of cartilage endplate stem cells (CESCs), while rapamycin-induced autophagy protected CESCs from TNF-α-induced oxidative stress and cell senescence...
March 6, 2019: Stem Cells
Barbara U Metzler-Zebeli, Sina-Catherine Siegerstetter, Elizabeth Magowan, Peadar G Lawlor, Niamh E O'Connell, Qendrim Zebeli
Restrictive feeding influences systemic metabolism of nutrients; however, this impact has not been evaluated in chickens of diverging feed efficiency. This study investigated the effect of ad libitum versus restrictive feeding (85% of ad libitum) on the serum metabolome and white blood cell composition in chickens of diverging residual feed intake (RFI; metric for feed efficiency). Blood samples were collected between days 33 and 37 post-hatch. While serum glucose was similar, serum uric acid and cholesterol were indicative of the nutritional status and chicken's RFI, respectively...
February 25, 2019: Metabolites
Francesca Nardi, Omar E Franco, Philip Fitchev, Alejandro Morales, Renee E Vickman, Simon W Hayward, Susan E Crawford
Acyl-CoA:diacylglycerol acyltransferase I (DGAT1) is a key enzyme in lipogenesis which is increased in metabolically active cells to meet nutrient requirements. DGAT1 has been recognized as an anti-obesity target; however, its role in the tumor microenvironment remains unclear. We postulated that, in prostate cancer (PCa) cells, augmented lipogenesis and growth are due to increased DGAT1 expression leading to microtubule-organizing center (MTOC) amplification. Thus, therapeutic targeting of DGAT1 potentially has tumor suppressive activity...
February 28, 2019: Scientific Reports
Gabriella M Forte, Elizabeth Davie, Shervi Lie, Mirita Franz-Wachtel, Ashley J Ovens, Tingting Wang, Jonathan S Oakhill, Boris Maček, Iain M Hagan, Janni Petersen
AMP-activated kinase (AMPK) and Target Of Rapamycin (TOR) signalling coordinate cell growth, proliferation, metabolism, and cell survival with the nutrient environment of cells. The poor vasculature and nutritional stress experienced by cells in solid tumours raises the question: how do they assimilate sufficient nutrients to survive? Here, we show that human and fission yeast cells import ATP and AMP from their external environment to regulate AMPK and TOR signalling. Exposure of fission yeast and human cells to external AMP impeded cell growth, however, in yeast this restraining impact required AMPK...
February 27, 2019: Journal of Cell Science
Jeff M P Holly, Kalina Biernacka, Claire M Perks
There has been a resurgence of interest in cancer metabolism; primarily in the resetting of metabolism within malignant cells. Metabolism within cells has always been a tightly regulated process; initially in protozoans due to metabolic enzymes, and the intracellular signaling pathways that regulate these, being directly sensitive to the availability of nutrients. With the evolution of metazoans many of these controls had been overlaid by extra-cellular regulators that ensured coordinated regulation of metabolism within the community of cells that comprised the organism...
2019: Frontiers in Endocrinology
Jonas Hauser, Sébastien Sultan, Andreas Rytz, Pascal Steiner, Nora Schneider
During the development of the central nervous system, oligodendrocytes (OLs) are responsible for myelination, the formation of the myelin sheath around axons. This process enhances neuronal connectivity and supports the maturation of emerging cognitive functions. In humans, recent evidence suggests that early life nutrition may affect myelination. In the present study, we investigated the impact of a blend containing docosahexaenoic acid, arachidonic acid, vitamin B12, vitamin B9, iron and sphingomyelin, or each of these nutrients individually, on oligodendrocyte precursor cells (OPCs) proliferation and maturation into OLs as well as their myelinating properties...
February 26, 2019: Nutritional Neuroscience
Roman Maslanka, Renata Zadrag-Tecza
Carbohydrates are dietary nutrients that have an influence on cells physiology, cell reproductive capacity and, consequently, the lifespan of organisms. They are used in cellular processes after conversion to glucose, which is the primary source of energy and carbon skeleton for biosynthetic processes. Studies of the influence of glucose on cellular parameters and lifespan of organisms are primarily concerned with the effect of low glucose concentration defined as calorie restriction conditions. However, the effect of high glucose concentration on cell physiology is also very important...
February 25, 2019: Journal of Cellular Physiology
Lennart Kuck, Marijke Grau, Wilhelm Bloch, Michael J Simmonds
The cellular deformability of red blood cells (RBC) is exceptional among mammalian cells and facilitates nutrient delivery throughout the microcirculation; however, this physical property is negatively impacted by oxidative stress. It remains unresolved whether the molecular determinants of cellular deformability - which in the contemporary model of RBC are increasingly recognized - are sensitive to free radicals. Moreover, given cellular deformability has recently been demonstrated to increase following exposure to specific doses of mechanical stimulation, the potential for using shear "conditioning" as a novel method to reverse free-radical induced impairment of cell mechanics is of interest...
2019: Frontiers in Physiology
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