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https://www.readbyqxmd.com/read/27899591/modulation-of-nonsense-mediated-decay-by-rapamycin
#1
Rocio T Martinez-Nunez, Andrew Wallace, Doyle Coyne, Linnea Jansson, Miles Rush, Hanane Ennajdaoui, Sol Katzman, Joanne Bailey, Katrin Deinhardt, Tilman Sanchez-Elsner, Jeremy R Sanford
Rapamycin is a naturally occurring macrolide whose target is at the core of nutrient and stress regulation in a wide range of species. Despite well-established roles as an inhibitor of cap-dependent mRNA translation, relatively little is known about its effects on other modes of RNA processing. Here, we characterize the landscape of rapamycin-induced post-transcriptional gene regulation. Transcriptome analysis of rapamycin-treated cells reveals genome-wide changes in alternative mRNA splicing and pronounced changes in NMD-sensitive isoforms...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895530/alpha-synuclein-contributes-to-malignant-progression-of-human-meningioma-via-the-akt-mtor-pathway
#2
Yiqin Ge, Kan Xu
BACKGROUND: The aim of this study is to explore the expression of alpha-synuclein (α-synuclein) in benign, atypical, and anaplastic meningiomas and determine its role in the malignant progression of meningiomas. METHODS: Expression of α-synuclein was measured in 44 meningioma samples by real-time PCR analysis. The effects of overexpression or knockdown of α-synuclein on meningioma cell growth, invasiveness, and tumorigenicity were determined. RESULTS: Atypical and anaplastic meningiomas displayed significantly greater levels of α-synuclein mRNA, relative to benign tumors...
2016: Cancer Cell International
https://www.readbyqxmd.com/read/27796683/akt-ampk-mtor-pathway-was-involved-in-the-autophagy-induced-by-vitamin-e-succinate-in-human-gastric-cancer-sgc-7901-cells
#3
Yang Yu, Liying Hou, Huacui Song, Peixiang Xu, Yue Sun, Kun Wu
Vitamin E succinate (VES), a derivative of vitamin E, is a promising cancer chemopreventive agent that inhibits tumor promotion by inducing apoptotic cell death. The effects of VES on autophagy, an intricate programmed process which helps cells survive in some stressed situations by degrading some cytoplasmic material, are unclear. When human gastric cancer cells SCG-7901 were exposed to VES, both the level of microtubule-associated protein 1 light chain 3 and the yeast ATG6 homolog Beclin-1 increased, and related autophagy genes were activated, thereby suggesting that autophagy was induced by VES...
October 28, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27763553/4ebp-dependent-signaling-supports-west-nile-virus-growth-and-protein-expression
#4
Katherine D Shives, Aaron R Massey, Nicholas A May, Thomas E Morrison, J David Beckham
West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an (m7)GpppNm 5' cap with 2'-O-methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1) for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown...
October 18, 2016: Viruses
https://www.readbyqxmd.com/read/27680387/interplay-between-cell-cycle-and-autophagy-induced-by-boswellic-acid-analog
#5
Anup S Pathania, Santosh K Guru, Suresh Kumar, Ashok Kumar, Masroor Ahmad, Shashi Bhushan, Parduman R Sharma, Priya Mahajan, Bhahwal A Shah, Simmi Sharma, Amit Nargotra, Ram Vishwakarma, Hasan Korkaya, Fayaz Malik
In this study, we investigated the role of autophagy induced by boswellic acid analog BA145 on cell cycle progression in pancreatic cancer cells. BA145 induced robust autophagy in pancreatic cancer cell line PANC-1 and exhibited cell proliferation inhibition by inducing cells to undergo G2/M arrest. Inhibition of G2/M progression was associated with decreased expression of cyclin A, cyclin B, cyclin E, cdc2, cdc25c and CDK-1. Pre-treatment of cells with autophagy inhibitors or silencing the expression of key autophagy genes abrogated BA145 induced G2/M arrest and downregulation of cell cycle regulatory proteins...
September 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27617277/the-akt-mtor-pathway-data-comparing-young-and-aged-mice-with-leucine-supplementation-at-the-onset-of-skeletal-muscle-regeneration
#6
Richard A Perry, Lemuel A Brown, David E Lee, Jacob L Brown, Jamie I Baum, Nicholas P Greene, Tyrone A Washington
The data described herein is related to the article "Differential Effects of Leucine Supplementation in Young and Aged Mice at the Onset of Skeletal Muscle Regeneration" [1]. Aging is associated with a decreased ability of skeletal muscle to regenerate following injury. Leucine supplementation has been extensively shown, in young subjects, to promote protein synthesis during regeneration; however, the effects of leucine supplementation on the Akt/mTOR pathway in aged mice at the onset of muscle regeneration are not fully elucidated...
September 2016: Data in Brief
https://www.readbyqxmd.com/read/27585465/sinomenine-attenuates-chronic-inflammatory-pain-in-mice
#7
Shuo Li, Jing Han, Dong-Sheng Wang, Qi Yang, Bin Feng, Wen-Bo Kang, Le Yang, Gang Liu, Ming-Gao Zhao
Sinomenine, an alkaloid originally isolated from the roots of Sinomeniumacutum, is used as a traditional Chinese medicine for rheumatic arthritis. However, little is known about the neuronal mechanisms underlying the analgesic effects of sinomenine in animals with chronic inflammatory pain. In this study, we investigated the persistent inflammatory pain induced by hind paw injection of complete Freund's adjuvant (CFA) in mice, which was reversed by sinomenine administration. In the anterior cingulate cortex (ACC), a region highly associated with chronic pain processing, the upregulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors and Ca(2+)/calmodulin-dependent protein kinase II, total levels of GluA1, and phosphorylation of GluA1 at Ser831 (p-GluA1-Ser831) were reversed by systemically administrating sinomenine...
September 1, 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/27575705/loss-of-strength-capacity-is-associated-with-mortality-but-resistance-exercise-training-promotes-only-modest-effects-during-cachexia-progression
#8
Willian das Neves, Christiano Robles Rodrigues Alves, Ney Robson de Almeida, Fátima Lúcia Rodrigues Guimarães, Paulo Rizzo Ramires, Patricia Chakur Brum, Antonio Herbert Lancha
AIMS: Resistance exercise training (RET) has been adopted as non-pharmacological anti-catabolic strategy. However, the role of RET to counteract cancer cachexia is still speculative. This study aimed to verify whether short-term RET would counteract skeletal muscle wasting in a severe cancer cachexia rat model. MAIN METHODS: Wistar rats were randomly allocated into four experimental groups; 1) untrained control rats (control), 2) rats submitted to RET (control+RET), 3) untrained rats injected with Walker 256 tumor cells in the bone marrow (tumor) and 4) rats injected with Walker 256 tumor cells in the bone marrow and submitted to RET (tumor+RET)...
October 15, 2016: Life Sciences
https://www.readbyqxmd.com/read/27525480/insulin-signaling-controls-neurotransmission-via-the-4ebp-dependent-modification-of-the-exocytotic-machinery
#9
Rebekah Elizabeth Mahoney, Jorge Azpurua, Benjamin A Eaton
Altered insulin signaling has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathy and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on neuronal function is incomplete. Here, we show that cell autonomous insulin signaling within the Drosophila CM9 motor neuron regulates the release of neurotransmitter via alteration of the synaptic vesicle fusion machinery. This effect of insulin utilizes the FOXO-dependent regulation of the thor gene, which encodes the Drosophila homologue of the eif-4e binding protein (4eBP)...
2016: ELife
https://www.readbyqxmd.com/read/27354468/braf-v600e-mutant-colorectal-cancer-subtypes-based-on-gene-expression
#10
David Barras, Edoardo Missiaglia, Pratyaksha Wirapati, Oliver M Sieber, Robert N Jorissen, Christopher Love, Peter L Molloy, Ian T Jones, Stephen McLaughlin, Peter Gibbs, Justin Guinney, Iris M Simon, Arnaud Roth, Fred T Bosman, Sabine Tejpar, Mauro Delorenzi
PURPOSE: Mutation of BRAF at the valine 600 residue occurs in ~10% of colorectal cancers (CRC), a group with particularly poor prognosis. The response of BRAF mutant CRC to recent targeted strategies such as anti-BRAF or combinations with MEK and EGFR inhibitors remains minimal and highly heterogeneous within BRAF V600E cohorts. There is clearly an unmet need in understanding the biology of BRAF V600E CRC and potential subgroups within this population. EXPERIMENTAL DESIGN: In the biggest yet reported cohort of 218 BRAF V600E with gene expression data, we performed unsupervised clustering using non-negative matrix factorization to identify gene expression based subgroups and characterized pathway activation...
June 27, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27343979/inhibitions-of-mtorc1-and-4ebp-1-are-key-events-orchestrated-by-rottlerin-in-sk-mel-28-cell-killing
#11
E Daveri, E Maellaro, G Valacchi, F Ietta, M Muscettola, E Maioli
Earlier studies demonstrated that Rottlerin exerts a time- and dose-dependent antiproliferative effect on SK-Mel-28 melanoma cells during 24 h of treatment, but cytotoxicity due to cell death began only after a 48 h exposure. In the current study, in order to identify the type of cell death in this cell line, which is notoriously refractory to most anticancer therapies, and to clarify the underlying mechanisms of this delayed outcome, we searched for apoptotic, necrotic/necroptotic and autophagic traits in Rottlerin-exposed cells...
September 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27327351/differential-effects-of-leucine-supplementation-in-young-and-aged-mice-at-the-onset-of-skeletal-muscle-regeneration
#12
Richard A Perry, Lemuel A Brown, David E Lee, Jacob L Brown, Jamie I Baum, Nicholas P Greene, Tyrone A Washington
Aging decreases the ability of skeletal muscle to respond to injury. Leucine has been demonstrated to target protein synthetic pathways in skeletal muscle thereby enhancing this response. However, the effect of aging on leucine-induced alterations in protein synthesis at the onset of skeletal muscle regeneration has not been fully elucidated. The purpose of this study was to determine if aging alters skeletal muscle regeneration and leucine-induced alterations in markers of protein synthesis. The tibialis anterior of young (3 months) and aged (24 months) female C57BL/6J mice were injected with either bupivacaine or PBS, and the mice were given ad libitum access to leucine-supplemented or normal drinking water...
July 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27323407/combined-administration-of-fucoidan-ameliorates-tumor-and-chemotherapy-induced-skeletal-muscle-atrophy-in-bladder-cancer-bearing-mice
#13
Meng-Chuan Chen, Wen-Lin Hsu, Pa-An Hwang, Yen-Lin Chen, Tz-Chong Chou
Cancer cachexia is characterized by anorexia, skeletal muscle atrophy, and systemic inflammation. Fucoidan extracted from brown algae exhibits anti-inflammatory and anticancer activities. However, whether fucoidan ameliorates tumour and chemotherapy-induced muscle atrophy and -related cachectic symptoms remains unknown. Compared with mice with bladder cancer treated with chemotherapy alone (TGC group), those treated with a combination of low molecular weight fucoidan (LMWF) and chemotherapy drugs such as gemcitabine and cisplatin (TGCF) showed a significant reduction of body weight loss, muscle atrophy, and intestinal injury and dysfunction...
June 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27272311/multiple-myeloma-cells-promote-migration-of-bone-marrow-mesenchymal-stem-cells-by-altering-their-translation-initiation
#14
Mahmoud Dabbah, Oshrat Attar-Schneider, Victoria Zismanov, Shelly Tartakover Matalon, Michael Lishner, Liat Drucker
The role of the bone marrow microenvironment in multiple myeloma pathogenesis and progression is well recognized. Indeed, we have shown that coculture of bone marrow mesenchymal stem cells from normal donors and multiple myeloma cells comodulated translation initiation. Here, we characterized the timeline of mesenchymal stem cells conditioning by multiple myeloma cells, the persistence of this effect, and the consequences on cell phenotype. Normal donor mesenchymal stem cells were cocultured with multiple myeloma cell lines (U266, ARP1) (multiple myeloma-conditioned mesenchymal stem cells) (1...
June 6, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27226530/microrna-214-reduces-insulin-like-growth-factor-1-igf-1-receptor-expression-and-downstream-mtorc1-signaling-in-renal-carcinoma-cells
#15
Falguni Das, Nirmalya Dey, Amit Bera, Balakuntalam S Kasinath, Nandini Ghosh-Choudhury, Goutam Ghosh Choudhury
Elevated IGF-1/insulin-like growth factor-1 receptor (IGF-1R) autocrine/paracrine signaling in patients with renal cell carcinoma is associated with poor prognosis of the disease independent of their von Hippel-Lindau (VHL) status. Increased expression of IGF-1R in renal cancer cells correlates with their potency of tumor development and progression. The mechanism by which expression of IGF-1R is increased in renal carcinoma is not known. We report that VHL-deficient and VHL-positive renal cancer cells possess significantly decreased levels of mature, pre-, and pri-miR-214 than normal proximal tubular epithelial cells...
July 8, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27171400/nutritional-geometric-profiles-of-insulin-igf-expression-in-drosophila-melanogaster
#16
Stephanie Post, Marc Tatar
Insulin/IGF signaling (IIS) in Drosophila melanogaster is propagated by eight Drosophila insulin-like peptides (dilps) and is regulated by nutrition. To understand how dietary protein and sugar affect dilp expression, we followed the analytical concepts of the Nutritional Geometric Framework, feeding Drosophila adults media comprised of seven protein-to-carbohydrate ratios at four caloric concentrations. Transcript levels of all dilps and three IIS-regulated genes were measured. Each dilp presented a unique pattern upon a bivariate plot of sugar and protein...
2016: PloS One
https://www.readbyqxmd.com/read/27157598/dietary-low-or-excess-levels-of-lipids-reduced-growth-performance-and-impaired-immune-function-and-structure-of-head-kidney-spleen-and-skin-in-young-grass-carp-ctenopharyngodon-idella-under-the-infection-of-aeromonas-hydrophila
#17
Pei-Jun Ni, Wei-Dan Jiang, Pei Wu, Yang Liu, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
Our study explored the effect of dietary lipids on growth and immunity and structure (head kidney, spleen and skin) of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp with an average initial weight of 261.41 ± 0.53 g were fed diets containing six graded levels of lipids at 5.9-80.1 g/kg diet for 8 weeks. After that, a challenge trial was conducted by injection of Aeromonas hydrophila over 2 weeks. The results indicated that compared with optimal lipids supplementation, low and excess levels of lipids down-regulated the mRNA levels of antimicrobial peptides, anti-inflammatory cytokines, inhibitor of κBα (IκBα) and ribosomal p70S6 kinase (S6K1), and up-regulated pro-inflammatory cytokines, nuclear factor κB p65 (NF-κB p65), NF-κB c-Rel (not p52), IκB kinase α (IKKα), IKKβ, IKKγ, and eIF4E-binding protein (4EBP) mRNA levels in the head kidney and spleen of young grass carp (P < 0...
August 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/26976208/mesenchymal-stem-cells-secretomes-affect-multiple-myeloma-translation-initiation
#18
H Marcus, O Attar-Schneider, M Dabbah, V Zismanov, S Tartakover-Matalon, M Lishner, L Drucker
Bone marrow mesenchymal stem cells' (BM-MSCs) role in multiple myeloma (MM) pathogenesis is recognized. Recently, we have published that co-culture of MM cell lines with BM-MSCs results in mutual modulation of phenotype and proteome (via translation initiation (TI) factors eIF4E/eIF4GI) and that there are differences between normal donor BM-MSCs (ND-MSCs) and MM BM-MSCs (MM-MSCs) in this crosstalk. Here, we aimed to assess the involvement of soluble BM-MSCs' (ND, MM) components, more easily targeted, in manipulation of MM cell lines phenotype and TI with specific focus on microvesicles (MVs) capable of transferring critical biological material...
June 2016: Cellular Signalling
https://www.readbyqxmd.com/read/26790279/-regulative-mechanisms-of-mammalian-target-of-rapamycin-signaling-pathway-in-glomerular-hypertrophy-in-diabetic-nephropathy-and-interventional-effects-of-chinese-herbal-medicine
#19
REVIEW
Jing-Jing Yang, Yan-ru Huang, Yi-gang Wan, Shan-mei Shen, Zhi-min Mao, Wei Wu, Jian Yao
Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy (DN), and its regulatory mechanism is closely related to mammalian target of rapamycin (mTOR) signaling pathway activity. mTOR includes mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase(Akt)/adenosine monophosphate activated protein kinase(AMPK), and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins(4EBP) and phosphoprotein 70 S6Kinase(p70S6K)...
August 2015: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/26747729/a-novel-rat-model-of-gestational-diabetes-induced-by-intrauterine-programming-is-associated-with-alterations-in-placental-signaling-and-fetal-overgrowth
#20
Evangelina Capobianco, Daiana Fornes, Ivana Linenberg, Theresa L Powell, Thomas Jansson, Alicia Jawerbaum
A family history of diabetes predisposes to gestational diabetes mellitus (GDM). We hypothesized that female offspring of rats with pre-gestational diabetes will develop GDM, a pathology associated with fetal overgrowth and altered placental signaling. We found normal glycemia and insulinemia in the offspring from pre-gestational diabetic rats at three months of age. However, consistent with GDM, maternal hyperglycemia and hyperinsulinemia and increased fetal weight were evident when compared to controls. In this intrauterine programmed GDM model, the placentas showed alterations in mTOR pathway: unchanged phosphorylation of 4EBP-1 and PKCα despite reduced total expression of 4EBP-1 and PKCα, and increased phosphorylation of SGK1...
February 15, 2016: Molecular and Cellular Endocrinology
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