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https://www.readbyqxmd.com/read/27922192/evidence-for-pipecolate-oxidase-in-mediating-protection-against-hydrogen-peroxide-stress
#1
Sathish Kumar Natarajan, Ezhumalai Muthukrishnan, Oleh Khalimonchuk, Justin L Mott, Donald F Becker
Pipecolate, an intermediate of the lysine catabolic pathway, is oxidized to Δ(1) -piperideine-6-carboxylate (P6C) by the flavoenzyme L-pipecolate oxidase (PIPOX). P6C spontaneously hydrolyzes to generate α-aminoadipate semialdehyde, which is then converted into α-aminoadipate acid by α-aminoadipatesemialdehyde dehydrogenase. L-pipecolate was previously reported to protect mammalian cells against oxidative stress. Here, we examined whether PIPOX is involved in the mechanism of pipecolate stress protection...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27911920/sirna-targeting-mtor-effectively-prevents-the-proliferation-and-migration-of-human-lens-epithelial-cells
#2
Chunmei Zhang, Jingjing Liu, Na Jin, Guiming Zhang, Yahui Xi, Hongling Liu
Posterior capsule opacification (PCO) is the most common complication that causes visual decrease after extracapsular cataract surgery. The primary cause of PCO formation is the proliferation of the residual lens epithelial cells (LECs). The mammalian target of rapamycin (mTOR) plays an important role in the growth and migration of LECs. In the current study, we used small interfering RNA (siRNA) to specifically attenuate mTOR in human lens epithelial B3 cells (HLE B3). We aimed to examine the effect of mTOR-siRNA on the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of HLE B3 cells and explore the underlying mechanisms...
2016: PloS One
https://www.readbyqxmd.com/read/27903651/t-cells-encountering-myeloid-cells-programmed-for-amino-acid-dependent-immunosuppression-use-rictor-mtorc2-for-proliferative-checkpoint-decisions
#3
Lee-Ann Van de Velde, Chitra Subramanian, Amber M Smith, Luke Barron, Joseph E Qualls, Geoffrey Neale, Adolfo Alfonso-Pecchio, Suzanne Jackowski, Charles O Rock, Thomas A Wynn, Peter J Murray
Modulation of T cell proliferation and function by immunoregulatory myeloid cells is an essential means of preventing self-reactivity and restoring tissue homeostasis. Consumption of amino acids such as arginine and tryptophan by immunoregulatory macrophages is one pathway that suppresses local T cell proliferation. Using a reduced complexity in vitro macrophage: T cell co-culture system, we show that macrophage Arginase-1 (Arg1) is the only factor required by M2 macrophages to block T cells in G1, and this effect is mediated by L-arginine elimination rather than metabolite generation...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27902464/expression-of-rab1a-is-upregulated-in-human-lung-cancer-and-associated-with-tumor-size-and-t-stage
#4
Xinxin Wang, Feng Liu, Xiaoyu Qin, Tinglei Huang, Bo Huang, Yanjie Zhang, Bin Jiang
Rab1A expression is associated with malignant phenotypes in several human tumors; however, the role of Rab1A in lung cancer is still unclear. In this study, we attempted to establish the role of Rab1A in major human lung cancer subtypes. Rab1A expression in different histological types of human lung cancer was analyzed in lung cancer tissues with paired adjacent noncancerous tissues and a large panel of lung cancer cell lines. The effect of Rab1A expression on multiple cancer-associated signaling pathways was also examined...
November 29, 2016: Aging
https://www.readbyqxmd.com/read/27894090/gremlin-promotes-retinal-pigmentation-epithelial-rpe-cell-proliferation-migration-and-vegf-production-via-activating-vegfr2-akt-mtorc2-signaling
#5
Yuan Liu, Zhijun Chen, Haixia Cheng, Juan Chen, Jing Qian
Retinopathy of prematurity (ROP) is characterized by late-phase pathologic retinal vasoproliferation. Gremlin is a novel vascular endothelial growth factors (VEGF) receptor 2 (VEGFR2) agonist and promotes angiogenic response. We demonstrated that gremlin expression was significantly increased in retinas of ROP model mice, which was correlated with VEGF upregulation. In retinal pigmentation epithelial (RPE) cells, gremlin activated VEGFR2-Akt-mTORC2 (mammalian target of rapamycin complex 2) signaling, and promoted cell proliferation, migration and VEGF production...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27884298/mhy1485-activates-mtor-and-protects-osteoblasts-from-dexamethasone
#6
Sai Zhao, Caiyun Chen, Shouguo Wang, Feng Ji, Yue Xie
Dexamethasone (Dex) exerts cytotoxic effects to cultured osteoblasts. The potential effect of MHY1485, a small-molecular mammalian target of rapamycin (mTOR) activator, against the process was studied here. In both osteoblastic MC3T3-E1 cells and primary murine osteoblasts, treatment with MHY1485 significantly ameliorated Dex-induced cell death and apoptosis. mTOR inhibition, through mTOR kinase inhibitor OSI-027 or mTOR shRNAs, abolished MHY1485-mediated osteoblast cytoprotection against Dex. Intriguingly, activation of mTOR complex (mTORC1), but not mTORC2, is required for MHY1485's anti-Dex activity...
December 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27869123/a-systems-study-reveals-concurrent-activation-of-ampk-and-mtor-by-amino-acids
#7
Piero Dalle Pezze, Stefanie Ruf, Annika G Sonntag, Miriam Langelaar-Makkinje, Philip Hall, Alexander M Heberle, Patricia Razquin Navas, Karen van Eunen, Regine C Tölle, Jennifer J Schwarz, Heike Wiese, Bettina Warscheid, Jana Deitersen, Björn Stork, Erik Fäßler, Sascha Schäuble, Udo Hahn, Peter Horvatovich, Daryl P Shanley, Kathrin Thedieck
Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational-experimental approach with text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR complex 2 (mTORC2) are acutely activated by aa-readdition in an mTORC1-independent manner...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27854154/small-gtpases-in-c-elegans-metabolism
#8
Daniel Z Bar, Chayki Charar, Yosef Gruenbaum
The mechanistic target of rapamycin (mTOR) is an evolutionary conserved protein with a serine/threonine kinase activity that regulates cell growth, proliferation, motility, survival, protein synthesis, autophagy and transcription. It is embedded in 2 large protein complexes: mTORC1 and mTORC2. Regulation of specific mTOR pathway functions depends on multiple GTPases, that act either as regulators of mTOR protein complexes, coupling energy availability with mTORC1 activity, or as downstream effectors of both mTORC1 and mTORC2...
November 17, 2016: Small GTPases
https://www.readbyqxmd.com/read/27849011/intrinsic-cellular-signaling-mechanisms-determine-the-sensitivity-of-cancer-cells-to-virus-induced-apoptosis
#9
Yunfei Wang, Dawei Li, Jian Luo, Guimei Tian, Lisa Y Zhao, Daiqing Liao
Cancer cells of epithelial and mesenchymal phenotypes exhibit different sensitivities to apoptosis stimuli, but the mechanisms underlying this phenomenon remain partly understood. We constructed a novel recombinant adenovirus expressing Ad12 E1A (Ad-E1A12) that can strongly induce apoptosis. Ad-E1A12 infection of epithelial cancer cells displayed dramatic detachment and apoptosis, whereas cancer cells of mesenchymal phenotypes with metastatic propensity were markedly more resistant to this virus. Notably, forced detachment of epithelial cells did not further sensitize them to Ad-E1A12-induced apoptosis, suggesting that cell detachment is a consequence rather than the cause of Ad-E1A12-induced apoptosis...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27826244/judicious-toggling-of-mtor-activity-to-combat-insulin-resistance-and-cancer-current-evidence-and-perspectives
#10
REVIEW
Pei Shi Ong, Louis Z Wang, Xiaoyun Dai, Sheng Hsuan Tseng, Shang Jun Loo, Gautam Sethi
The mechanistic target of rapamycin (mTOR), via its two distinct multiprotein complexes, mTORC1, and mTORC2, plays a central role in the regulation of cellular growth, metabolism, and migration. A dysregulation of the mTOR pathway has in turn been implicated in several pathological conditions including insulin resistance and cancer. Overactivation of mTORC1 and disruption of mTORC2 function have been reported to induce insulin resistance. On the other hand, aberrant mTORC1 and mTORC2 signaling via either genetic alterations or increased expression of proteins regulating mTOR and its downstream targets have contributed to cancer development...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27825091/ikbke-protein-activates-akt-independent-of-phosphatidylinositol-3-kinase-pdk1-mtorc2-and-the-pleckstrin-homology-domain-to-sustain-malignant-transformation
#11
Jian-Ping Guo, Domenico Coppola, Jin Q Cheng
No abstract text is available yet for this article.
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27812539/mfge8-regulates-enterocyte-lipid-storage-by-promoting-enterocyte-triglyceride-hydrolase-activity
#12
Amin Khalifeh-Soltani, Deepti Gupta, Arnold Ha, Jahangir Iqbal, Mahmood Hussain, Michael J Podolsky, Kamran Atabai
The small intestine has an underappreciated role as a lipid storage organ. Under conditions of high dietary fat intake, enterocytes can minimize the extent of postprandial lipemia by storing newly absorbed dietary fat in cytoplasmic lipid droplets. Lipid droplets can be subsequently mobilized for the production of chylomicrons. The mechanisms that regulate this process are poorly understood. We report here that the milk protein Mfge8 regulates hydrolysis of cytoplasmic lipid droplets in enterocytes after interacting with the αvβ3 and αvβ5 integrins...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27807348/mtorc1-and-mtorc2-regulate-skin-morphogenesis-and-epidermal-barrier-formation
#13
Xiaolei Ding, Wilhelm Bloch, Sandra Iden, Markus A Rüegg, Michael N Hall, Maria Leptin, Linda Partridge, Sabine A Eming
Mammalian target of rapamycin (mTOR), a regulator of growth in many tissues, mediates its activity through two multiprotein complexes, mTORC1 or mTORC2. The role of mTOR signalling in skin morphogenesis and epidermal development is unknown. Here we identify mTOR as an essential regulator in skin morphogenesis by epidermis-specific deletion of Mtor in mice (mTOR(EKO)). mTOR(EKO) mutants are viable, but die shortly after birth due to deficits primarily during the early epidermal differentiation programme and lack of a protective barrier development...
October 27, 2016: Nature Communications
https://www.readbyqxmd.com/read/27799302/proliferating-helper-t-cells-require-rictor-mtorc2-to-integrate-signals-from-limiting-environmental-amino-acids
#14
Lee-Ann Van de Velde, Peter J Murray
Antigen-stimulated T cells require elevated importation of essential and non-essential amino acids to generate large numbers of daughter cells necessary for effective immunity to pathogens. When amino acids are limiting, T cells arrest in the G1 phase of the cell cycle, suggesting they have specific sensing mechanisms to ensure sufficient amino acids are available for multiple rounds of daughter generation. We found activation of mTORC1, which is regulated by amino acid amounts, was uncoupled from limiting amino acids in the G1 phase of the cell cycle...
October 31, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27789731/evaluation-of-akt-and-rictor-expression-levels-in-astrocytomas-of-all-grades
#15
Arthur William Alvarenga, Luis Eduardo Machado, Bruna Roz Rodrigues, Fernanda Cristina Sulla Lupinacci, Paulo Sanemastu, Eduardo Matta, Martín Roffé, Luís Fernando Bleggi Torres, Isabela Werneck da Cunha, Vilma Regina Martins, Glaucia Noeli Maroso Hajj
The mammalian target of rapamycin (mTOR) binds to several protein partners and forms two complexes, termed mTOR complexes 1 and 2 (mTORC1/2), that differ in components, substrates, and regulation. mTORC2 contains the protein Rapamycin-insensitive companion of mTOR (RICTOR); phosphorylates kinases of the AGC family, such as Akt; and controls the cytoskeleton. Even though the regulation of mTORC2 activity remains poorly understood, the hyperactivation of this signaling pathway has been shown to contribute to the oncogenic properties of gliomas in experimental models...
October 27, 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/27777073/mtorc2-activation-is-regulated-by-the-urokinase-receptor-upar-in-bladder-cancer
#16
Andrew M Hau, Mariah Z Leivo, Andrew S Gilder, Jing-Jing Hu, Steven L Gonias, Donna E Hansel
Mammalian target of rapamycin complex 2 (mTORC2) has been identified as a major regulator of bladder cancer cell migration and invasion. Upstream pathways that mediate mTORC2 activation remain poorly defined. Urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored membrane protein and known activator of cell-signaling. We identified increased uPAR expression in 94% of invasive human bladder cancers and in 54-71% of non-invasive bladder cancers, depending on grade. Normal urothelium was uPAR-immunonegative...
October 21, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27760338/metabolic-reprogramming-mediated-by-the-mtorc2-irf4-signaling-axis-is-essential-for-macrophage-alternative-activation
#17
Stanley Ching-Cheng Huang, Amber M Smith, Bart Everts, Marco Colonna, Erika L Pearce, Joel D Schilling, Edward J Pearce
Macrophage activation status is intrinsically linked to metabolic remodeling. Macrophages stimulated by interleukin 4 (IL-4) to become alternatively (or, M2) activated increase fatty acid oxidation and oxidative phosphorylation; these metabolic changes are critical for M2 activation. Enhanced glucose utilization is also characteristic of the M2 metabolic signature. Here, we found that increased glucose utilization is essential for M2 activation. Increased glucose metabolism in IL-4-stimulated macrophages required the activation of the mTORC2 pathway, and loss of mTORC2 in macrophages suppressed tumor growth and decreased immunity to a parasitic nematode...
October 18, 2016: Immunity
https://www.readbyqxmd.com/read/27758884/mtorc2-signaling-drives-the-development-and-progression-of-pancreatic-cancer
#18
David R Driscoll, Saadia A Karim, Makoto Sano, David M Gay, Wright Jacob, Jun Yu, Yusuke Mizukami, Aarthi Gopinathan, Duncan I Jodrell, T R Jeffry Evans, Nabeel Bardeesy, Michael N Hall, Brian J Quattrochi, David S Klimstra, Simon T Barry, Owen J Sansom, Brian C Lewis, Jennifer P Morton
mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27748764/mtorc1-and-mtorc2-in-cancer-and-the-tumor-microenvironment
#19
L C Kim, R S Cook, J Chen
The mammalian target of rapamycin (mTOR) is a crucial signaling node that integrates environmental cues to regulate cell survival, proliferation and metabolism, and is often deregulated in human cancer. mTOR kinase acts in two functionally distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), whose activities and substrate specificities are regulated by complex co-factors. Deregulation of this centralized signaling pathway has been associated with a variety of human diseases including diabetes, neurodegeneration and cancer...
October 17, 2016: Oncogene
https://www.readbyqxmd.com/read/27746127/the-calcineurin-variant-cna%C3%AE-1-controls-mouse-embryonic-stem-cell-differentiation-by-directing-mtorc2-membrane-localization-and-activation
#20
Jesús M Gómez-Salinero, Marina M López-Olañeta, Paula Ortiz-Sánchez, Javier Larrasa-Alonso, Alberto Gatto, Leanne E Felkin, Paul J R Barton, Inmaculada Navarro-Lérida, Miguel Ángel Del Pozo, Pablo García-Pavía, Balaji Sundararaman, Giovanna Giovinazo, Gene W Yeo, Enrique Lara-Pezzi
Embryonic stem cells (ESC) have the potential to generate all the cell lineages that form the body. However, the molecular mechanisms underlying ESC differentiation and especially the role of alternative splicing in this process remain poorly understood. Here, we show that the alternative splicing regulator MBNL1 promotes generation of the atypical calcineurin Aβ variant CnAβ1 in mouse ESCs (mESC). CnAβ1 has a unique C-terminal domain that drives its localization mainly to the Golgi apparatus by interacting with Cog8...
November 17, 2016: Cell Chemical Biology
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