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Cells Signaling Nutrients

Bohye Park, Joo Weon Lim, Hyeyoung Kim
Helicobacter pylori (H pylori) colonizes the human stomach and increases the risk of gastric diseases including gastric cancer. H pylori increases reactive oxygen species (ROS), which activate Janus-activator kinase 1 (Jak1)/signal transducers and activators of transcription 3 (Stat3) in gastric epithelial cells. ROS mediate hyperproliferation, a hallmark of carcinogenesis, by activating Wnt/β-catenin signaling in various cells. Lycopene is a potent antioxidant exhibiting anticancer effects. We hypothesized that lycopene may inhibit H pylori-induced hyperproliferation by suppressing ROS-mediated activation of Jak1/Stat3 and Wnt/β-catenin signaling, and β-catenin target gene expression in gastric epithelial cells...
July 21, 2018: Nutrition Research
Geoffrey G Hesketh, Lena Wartosch, Luther J Davis, Nicholas A Bright, J Paul Luzio
In addition to being the terminal degradative compartment of the cell's endocytic and autophagic pathways, the lysosome is a multifunctional signalling hub integrating the cell's response to nutrient status and growth factor/hormone signalling. The cytosolic surface of the limiting membrane of the lysosome is the site of activation of the multiprotein complex mammalian target of rapamycin complex 1 (mTORC1), which phosphorylates numerous cell growth-related substrates, including transcription factor EB (TFEB)...
2018: Progress in Molecular and Subcellular Biology
Maria Podinovskaia, Anne Spang
Endocytosis is a means for the cell to sample its environment for nutrients and regulate plasma membrane (PM) composition and area. Whereas the majority of internalized cargo is recycled back to the cell surface, select material is sent to the lysosome for degradation. Endosomes further play major roles in central cell activities as diverse as establishment of cell polarity and signaling, lysosomal storage and immunity. The complexity of endosomal functions is reflected by the extensive changes to endosome properties as they mature...
2018: Progress in Molecular and Subcellular Biology
Brendan T Finicle, Vaishali Jayashankar, Aimee L Edinger
While cancer cell proliferation depends on access to extracellular nutrients, inadequate tumour perfusion means that glucose, amino acids and lipids are often in short supply. To overcome this obstacle to growth, cancer cells utilize multiple scavenging strategies, obtaining macromolecules from the microenvironment and breaking them down in the lysosome to produce substrates for ATP generation and anabolism. Recent studies have revealed four scavenging pathways that support cancer cell proliferation in low-nutrient environments: scavenging of extracellular matrix proteins via integrins, receptor-mediated albumin uptake and catabolism, macropinocytic consumption of multiple components of the tumour microenvironment and the engulfment and degradation of entire live cells via entosis...
August 10, 2018: Nature Reviews. Cancer
Natalia V Varlakhanova, Bryan A Tornabene, Marijn G J Ford
The highly conserved TORC1 complex controls cell growth in response to nutrients, especially amino acids. EGO Complex activates TORC1 in response to glutamine and leucine. Here, we demonstrate that the I-BAR domain-containing protein Ivy1 colocalizes with Gtr1 and Gtr2, a heterodimer of small GTPases that are part of EGO Complex. Ivy1 is a negative regulator of Gtr-induced TORC1 activation. Ivy1 is contained within puncta associated with the vacuolar membrane in cells grown in rich medium or after brief nitrogen starvation...
August 10, 2018: Journal of Cell Science
Warren A Vieira, Kaylee M Wells, Roni Milgrom, Catherine D McCusker
Urodele amphibians such as the axolotl regenerate complete limbs as adults, and understanding how the "blueprint", or pattern, of the regenerate is established and manipulated are areas of intense interest. Nutrient signaling plays an important role in pattern formation during regeneration. Retinoic acid signaling is the most characterized pathway during this process. Exogenous retinoic acid (RA) reprograms the pattern information in regenerating cells to a more posterior, ventral, and proximal identity...
August 7, 2018: Mechanisms of Development
Fengjun Guo, Haina Zhang, Zanhui Jia, Manhua Cui, Jingyan Tian
Endometrial cancer tends to be an aggressive malignancy. Although the disease prognosis can be good at the early stages of disease, the advanced condition is not curable. Chemotherapy regimens and hormone-based therapy in combination with surgery are major approaches for the management of endometrial cancers. However, intrinsic chemoresistance reduces the success rate and increases the possibility of disease relapse. Investigation of underlying mechanisms revealed altered activation of PI3K/AKT, MAPK, fibroblast growth factor (FGF), mTOR and WNT pathways and reduced gene expression of tumor suppressor p53 in recurrent endometrial cancer...
2018: American Journal of Cancer Research
Natalia Bravo-Santano, James K Ellis, Luis M Mateos, Yolanda Calle, Hector C Keun, Volker Behrends, Michal Letek
Staphylococcus aureus is a facultative intracellular pathogen that invades and replicates within many types of phagocytic and nonphagocytic cells. During intracellular infection, S. aureus is capable of subverting xenophagy and escaping to the cytosol of the host cell. Furthermore, drug-induced autophagy facilitates the intracellular replication of S. aureus , but the reasons behind this are unclear. Here, we have studied the host central carbon metabolism during S. aureus intracellular infection. We found extensive metabolic rerouting and detected several distinct metabolic changes that suggested starvation-induced autophagic flux in infected cells...
August 8, 2018: MSphere
Paulo A Gameiro, Kevin Struhl
Nutrient deprivation inhibits mRNA translation through mTOR and eIF2α signaling, but it is unclear how the translational program is controlled to reflect the degree of a metabolic stress. In a model of breast cellular transformation, various forms of nutrient deprivation differentially affect the rate of protein synthesis and its recovery over time. Genome-wide translational profiling of glutamine-deprived cells reveals a rapid upregulation of mRNAs containing uORFs and downregulation of ribosomal protein mRNAs, which are followed by selective translation of cytokine and inflammatory mRNAs...
August 7, 2018: Cell Reports
Kat S Moore, Marieke von Lindern
Control of gene expression in erythropoiesis has to respond to signals that may emerge from intracellular processes or environmental factors. Control of mRNA translation allows for relatively rapid modulation of protein synthesis from the existing transcriptome. For instance, the protein synthesis rate needs to be reduced when reactive oxygen species or unfolded proteins accumulate in the cells, but also when iron supply is low or when growth factors are lacking in the environment. In addition, regulation of mRNA translation can be important as an additional layer of control on top of gene transcription, in which RNA binding proteins (RBPs) can modify translation of a set of transcripts to the cell's actual protein requirement...
2018: Frontiers in Physiology
Toni Petan, Eva Jarc, Maida Jusović
Cancer cells possess remarkable abilities to adapt to adverse environmental conditions. Their survival during severe nutrient and oxidative stress depends on their capacity to acquire extracellular lipids and the plasticity of their mechanisms for intracellular lipid synthesis, mobilisation, and recycling. Lipid droplets, cytosolic fat storage organelles present in most cells from yeast to men, are emerging as major regulators of lipid metabolism, trafficking, and signalling in various cells and tissues exposed to stress...
August 3, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Heon-Woo Lee, Pengchun Yu, Michael Simons
The blood and lymphatic vasculatures are vital to the maintenance of homeostasis. The interaction between two vascular networks throughout the body is precisely controlled to enable oxygen and nutrient delivery, removal of carbon dioxide and metabolic waste, drainage of interstitial fluid, transport of immune cells, and other key activities. Recent years have seen an explosion of information dealing with the development and function of the lymphatic system. The growth of lymphatic vessels, termed lymphangiogenesis, is a high-energy requirement process that involves sprouting, proliferation, migration, and remodeling of lymphatic endothelial cells and capillaries...
2018: F1000Research
Mary Priyanka Udumula, Audesh Bhat, Sureshbabu Mangali, Jaspreet Kalra, Indu Dhar, Dharamrajan Sriram, Arti Dhar
AIMS: Double stranded protein kinase R cellular response is associated with various stress signals such as nutrients, endoplasmic stress, cytokines and mechanical stress. Increased PKR activity has been observed under diabetic and cardiovascular disease conditions. Most of the currently available PKR inhibitors are non-specific and have other effects as well. Thus, the aim of the present study was to examine the effect of novel PKR inhibitor indirubin-3-hydrazone (IHZ) in cultured rat H9C2 cardiomyocytes and wistar rats...
August 1, 2018: Life Sciences
Sydney L Campbell, Kathryn E Wellen
Nutrient-sensing mechanisms ensure that cellular activities are coordinated with nutrient availability. Recent work has established links between metabolite pools and protein post-translational modifications, as metabolites are substrates of enzymes that add or remove modifications such as acetylation, methylation, and glycosylation. Cancer cells undergo metabolic reprogramming and exhibit metabolic plasticity that allows them to survive and proliferate within the tumor microenvironment. In this article we review the evidence that, in cancer cells, nutrient availability and oncogenic metabolic reprogramming impact the abundance of key metabolites that regulate signaling and epigenetics...
August 2, 2018: Molecular Cell
Joshua N Farr, Maria Almeida
Aging research has undergone unprecedented advances at an accelerating rate in recent years, leading to excitement in the field as well as opportunities for imagination and innovation. Novel insights indicate that, rather than resulting from a pre-programmed series of events, the aging process is predominantly driven by fundamental non-adaptive mechanisms that are interconnected, linked, and overlap. To varying degrees, these mechanisms also manifest with aging in bone where they cause skeletal fragility. Because these mechanisms of aging can be manipulated, it might be possible to slow, delay, or alleviate multiple age-related diseases and their complications by targeting conserved genetic signaling pathways, controlled functional networks, and basic biochemical processes...
August 3, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Shaopu Wang, Susanne Meese, Susanne E Ulbrich, Heinrich Bollwein, Monika Röntgen, Ulrike Gimsa, Angela Schwarm
This in vitro study examined the ability of important immune modulators [β-hydroxybutyrate (BHB), cortisol, prolactin, isoproterenol and insulin] to influence the responsiveness of peripheral blood mononuclear cells (PBMC) from multiparous dairy cows 29 ± 2 days before and 14 ± 3 days after calving. The activation and proliferation of PBMC in response to the mitogen phytohemagglutinin was estimated by the oxygen consumption rate after 24 hr and the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5diphenyl tetrazolium bromide) method after 72 hr respectively...
August 3, 2018: Journal of Animal Physiology and Animal Nutrition
Kerrie E McNally, Peter J Cullen
Endosomes are major protein sorting stations in cells. Endosomally localised multi-protein complexes sort integral proteins, including signaling receptors, nutrient transporters, adhesion molecules, and lysosomal hydrolase receptors, for lysosomal degradation or conversely for retrieval and subsequent recycling to various membrane compartments. Correct endosomal sorting of these proteins is essential for maintaining cellular homeostasis, with defects in endosomal sorting implicated in various human pathologies including neurodegenerative disorders...
July 30, 2018: Trends in Cell Biology
Rolake O Alabi, Gregory Farber, Carl P Blobel
The vasculature is a remarkably interesting, complex, and interconnected organ. It provides a conduit for oxygen and nutrients, filtration of waste products, and rapid communication between organs. Much remains to be learned about the specialized vascular beds that fulfill these diverse, yet vital functions. This review was prompted by the discovery that Notch signaling in mouse endothelial cells is crucial for the development of specialized vascular beds found in the heart, kidneys, liver, intestines, and bone...
October 1, 2018: Physiological Reviews
Max C Petersen, Gerald I Shulman
The 1921 discovery of insulin was a Big Bang from which a vast and expanding universe of research into insulin action and resistance has issued. In the intervening century, some discoveries have matured, coalescing into solid and fertile ground for clinical application; others remain incompletely investigated and scientifically controversial. Here, we attempt to synthesize this work to guide further mechanistic investigation and to inform the development of novel therapies for type 2 diabetes (T2D). The rational development of such therapies necessitates detailed knowledge of one of the key pathophysiological processes involved in T2D: insulin resistance...
October 1, 2018: Physiological Reviews
Nabanita Bhattacharyya, Irene Nailain Nkumama, Zaccheus Newland-Smith, Li-Ying Lin, Wen Yin, Rebecca E Cullen, Jack S Griffiths, Alexander R Jarvis, Michael J Price, Pei Ying Chong, Russell Wallis, Helen M O'Hare
Signaling by serine/threonine phosphorylation controls diverse processes in bacteria, and identification of the stimuli that activate protein kinases is an outstanding question in the field. Recently, we showed that nutrients stimulate phosphorylation of the protein kinase G substrate GarA in Mycobacterium smegmatis and Mycobacterium tuberculosis and that the action of GarA in regulating central metabolism depends upon whether it is phosphorylated. Here we present an investigation into the mechanism by which nutrients activate PknG...
July 31, 2018: MBio
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