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https://www.readbyqxmd.com/read/28223222/disrupting-the-key-circadian-regulator-clock-leads-to-age-dependent-cardiovascular-disease
#1
Faisal J Alibhai, Jonathan LaMarre, Cristine J Reitz, Elena V Tsimakouridze, Jeffrey T Kroetsch, Steffen-Sebastian Bolz, Alex Shulman, Samantha Steinberg, Thomas P Burris, Gavin Y Oudit, Tami A Martino
The circadian mechanism underlies daily rhythms in cardiovascular physiology and rhythm disruption is a major risk factor for heart disease and worse outcomes. However, the role of circadian rhythms is generally clinically unappreciated. Clock is a core component of the circadian mechanism and here we examine the role of Clock as a vital determinant of cardiac physiology and pathophysiology in aging. Clock(Δ19/Δ19) mice develop age-dependent increases in heart weight, hypertrophy, dilation, impaired contractility, and reduced myogenic responsiveness...
February 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28218391/mapk3-1-participates-in-the-activation-of-primordial-follicles-through-mtorc1-kitl-signaling
#2
Yu Zhao, Yu Zhang, Jia Li, Nana Zheng, Xiaoting Xu, Jing Yang, Guoliang Xia, Meijia Zhang
The majority of ovarian primordial follicles are preserved in a dormant state to maintain the female reproductive lifespan, and only a few primordial follicles are activated to enter the growing follicle pool in each wave. Recent studies have shown that primordial follicular activation depends on mammalian target of rapamycin complex 1 (mTORC1)-KIT ligand (KITL) signaling in pre-granulosa cells and its receptor (KIT)-phosphoinositol 3 kinase (PI3K) signaling in oocytes. However, the upstream regulator of mTORC1 signaling is unclear...
February 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28216662/ddx5-promotes-gastric-cancer-cell-proliferation-in-vitro-and-in-vivo-through-mtor-signaling-pathway
#3
Cheng Du, Dan-Qi Li, Na Li, Li Chen, Shi-Sen Li, Yang Yang, Ming-Xiao Hou, Man-Jiang Xie, Zhen-Dong Zheng
DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) is an ATP-dependent RNA helicase that is overexpressed in various malignancies. Increasing evidence suggests that DDX5 participates in carcinogenesis and cancer progression via promoting cell proliferation and metastasis. However, the functional role of DDX5 in gastric cancer is largely unknown. In this study, we observed that DDX5 was significantly up-regulated in gastric cancer tissues compared with the paired adjacent normal tissues. The expression of DDX5 correlated strongly with Ki67 index and pathological stage of gastric cancer...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28214828/role-for-target-of-rapamycin-mtor-signal-pathway-in-regulating-neuronal-injury-after-intracerebral-hemorrhage
#4
Jie-Ping Wang, Meng-Yu Zhang
BACKGROUND/AIMS: Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR signal and its downstream products to brain injuries induced by intracerebral hemorrhage (ICH) in rats. METHODS: Western Blot analysis was employed to examine the protein expression of mTOR and its downstream pathway and Caspase-3...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28193461/gill-structural-integrity-changes-in-fish-deficient-or-excessive-in-dietary-isoleucine-towards-the-modulation-of-tight-junction-protein-inflammation-apoptosis-and-antioxidant-defense-via-nf-%C3%AE%C2%BAb-tor-and-nrf2-signaling-pathways
#5
Lin Feng, Lu Gan, Wei-Dan Jiang, Pei Wu, Yang Liu, Jun Jiang, Ling Tang, Sheng-Yao Kuang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study firstly aimed to test the impact of dietary isoleucine (Ile) on tight junction protein, inflammation, apoptosis, antioxidant defense and related signaling molecule gene expression in the gill of fish. Young grass carp (Ctenopharyngodon idella) (weighing 256.8 ± 3.5 g) were fed six diets containing graded levels of Ile, namely, 3.8, 6.6, 9.3, 12.5, 15.2 and 18.5 g/kg diet for 8 weeks. The results firstly revealed that Ile deficiency down-regulated the mRNA expressions of claudin-3, claudin-b, claudin-c, occludin and zonula occludens-1 (ZO-1) and up-regulated the mRNA expression of claudin-12, which led to the intercellular structure damage of fish gill...
February 11, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28184936/inhibition-of-rab1a-suppresses-epithelial-mesenchymal-transition-and-proliferation-of-triple-negative-breast-cancer-cells
#6
Hui Xu, Mingping Qian, Bingkun Zhao, Chenyang Wu, Niraj Maskey, Hongming Song, Dengfeng Li, Jialu Song, Kaiyao Hua, Lin Fang
RAB1A acts as an oncogene in various cancers, and emerging evidence has verified that RAB1A is an mTORC1 activator in hepatocellular and colorectal cancer, but the role of RAB1A in breast cancer remains unclear. In this investigation, RAB1A siRNA was successfully transfected in MDA-MB-231 and BT-549 human triple-negative breast cancer cells, and verified by real‑time quantitative polymerase chain reaction and western blotting. Then, MTT cell proliferation, colony formation, cell invasion and wound healing assays were performed to characterize the function of RAB1A in the breast cancer cell lines...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28183860/diminished-satellite-cell-fusion-and-s6k1-expression-in-myotubes-derived-from-skeletal-muscle-of-low-birth-weight-neonatal-pigs
#7
Ying Chen, Haibo Zhu, Sydney R McCauley, Lidan Zhao, Sally E Johnson, Robert P Rhoads, Samer W El-Kadi
Low birth weight (LBWT) is consistently associated with impaired postnatal muscle growth in mammals. Satellite cell (SC)-mediated myonuclear incorporation precedes protein accumulation in the early stages of postnatal muscle development and growth. The objective of this study was to investigate proliferation and differentiation of SCs and the regulation of protein synthesis signaling in response to insulin-like growth factor (IGF)-I stimulation in SC-derived myotubes of LBWT neonatal pigs. SCs isolated from Longissimus dorsi muscle of LBWT and NBWT pigs (3-d-old, n = 8) were cultured and induced to proliferate and differentiate to myotubes in vitro...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28178239/eprs-is-a-critical-mtorc1-s6k1-effector-that-influences-adiposity-in-mice
#8
Abul Arif, Fulvia Terenzi, Alka A Potdar, Jie Jia, Jessica Sacks, Arnab China, Dalia Halawani, Kommireddy Vasu, Xiaoxia Li, J Mark Brown, Jie Chen, Sara C Kozma, George Thomas, Paul L Fox
Metabolic pathways that contribute to adiposity and ageing are activated by the mammalian target of rapamycin complex 1 (mTORC1) and p70 ribosomal protein S6 kinase 1 (S6K1) axis. However, known mTORC1-S6K1 targets do not account for observed loss-of-function phenotypes, suggesting that there are additional downstream effectors of this pathway. Here we identify glutamyl-prolyl-tRNA synthetase (EPRS) as an mTORC1-S6K1 target that contributes to adiposity and ageing. Phosphorylation of EPRS at Ser999 by mTORC1-S6K1 induces its release from the aminoacyl tRNA multisynthetase complex, which is required for execution of noncanonical functions of EPRS beyond protein synthesis...
February 16, 2017: Nature
https://www.readbyqxmd.com/read/28153047/arginase-i-enhances-vascular-endothelial-inflammation-and-senescence-through-enos-uncoupling
#9
Cuicui Zhu, Yi Yu, Jean-Pierre Montani, Xiu-Fen Ming, Zhihong Yang
BACKGROUND: Augmented arginase-II (Arg-II) is implicated in endothelial senescence and inflammation through a mutual positive regulatory circuit with S6K1. This study was conducted to investigate whether Arg-I, another isoform of arginase that has been also reported to play a role in vascular endothelial dysfunction, promotes endothelial senescence through similar mechanisms. RESULTS: The non-senescent human endothelial cells from umbilical veins (passage 2 to 4) were transduced with empty recombinant adenovirus vector (rAd/CMV) as control or rAd/CMV-Arg-I to overexpress Arg-I...
February 2, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28153010/targeting-muc1-c-inhibits-the-akt-s6k1-elf4a-pathway-regulating-tigar-translation-in-colorectal-cancer
#10
Rehan Ahmad, Maroof Alam, Masanori Hasegawa, Yasumitsu Uchida, Omar Al-Obaid, Surender Kharbanda, Donald Kufe
BACKGROUND: Colorectal cancer is third most common malignancy and is the second most common cause of cancer-related death. The MUC1 heterodimeric protein is aberrantly overexpressed in colorectal cancer and has been linked to poor outcomes in this disease. Here, we investigate the effects of the MUC1-C subunit inhibitor (GO-203), which disrupts MUC1-C homo-oligomerization, on human colorectal cancer cells. METHODS: TIGAR mRNA level was determined using qRT-PCR. Western blotting was used to measure TIGAR protein level and AKT-mTOR-S6K1 pathways...
February 2, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28118364/physical-and-flavor-characteristics-fatty-acid-profile-antioxidant-status-and-nrf2-dependent-antioxidant-enzyme-gene-expression-changes-in-young-grass-carp-ctenopharyngodon-idella-fillets-fed-dietary-valine
#11
Jian-Bo Luo, Lin Feng, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study was conducted to examine the effects of dietary valine on the physical and flavor characteristics, fatty acid (FA) profile, antioxidant status and Nrf2-dependent antioxidant enzyme gene expression in the muscle of young grass carp (Ctenopharyngodon idella) fed increasing levels of valine (4.3, 8.0, 10.6, 13.1, 16.9 and 19.1 g/kg) for 8 weeks. Compared with the control group, the group fed valine showed improved physical characteristics of fish fillets (increased relative shear force, hydroxyproline, protein and lipid levels and decreased cathepsin B and L activities, as well as cooking loss, were observed)...
2017: PloS One
https://www.readbyqxmd.com/read/28100477/inability-to-replete-white-adipose-tissue-during-the-recovery-phase-of-sepsis-is-associated-with-increased-autophagy-apoptosis-and-proteasome-activity
#12
Kristen T Crowell, David I Soybel, Charles H Lang
Adipose tissue is an important energy depot and endocrine organ, and the degree of adiposity impacts the host response to infection. However, little is known regarding the mechanisms by which white adipose tissue (WAT) is lost acutely and then restored after resolution of sepsis. Therefore, signaling pathways governing protein synthesis, autophagy, apoptosis and the ubiquitin-proteasome were investigated to identify potential mechanisms mediating the acute (24 h) loss of WAT after cecal ligation and puncture (CLP) as well as the failure to replenish WAT during recovery (day 10)...
January 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28081222/at7867-inhibits-human-colorectal-cancer-cells-via-akt-dependent-and-akt-independent-mechanisms
#13
Shihu Zhang, Zhengming Deng, Chen Yao, Ping Huang, Yi Zhang, Shibing Cao, Xiangcheng Li
AKT is often hyper-activated in human colorectal cancers (CRC). This current study evaluated the potential anti-CRC activity by AT7867, a novel AKT and p70S6K1 (S6K1) dual inhibitor. We showed that AT7867 inhibited survival and proliferation of established (HT-29, HCT116 and DLD-1 lines) and primary human CRC cells. Meanwhile, it provoked caspase-dependent apoptosis in the CRC cells. Molecularly, AT7867 blocked AKT-S6K1 activation in CRC cells. Restoring AKT-S6K1 activation, via expression of a constitutively-active AKT1 ("ca-AKT1"), only partially attenuated AT7867-induced HT-29 cell death...
2017: PloS One
https://www.readbyqxmd.com/read/28078713/the-novel-mtor-complex-1-2-inhibitor-p529-inhibits-human-lung-myofibroblast-differentiation
#14
Keith T Ferguson, Elizabeth E Torr, Ksenija Bernau, Jonathan Leet, Davis Sherris, Nathan Sandbo
Idiopathic pulmonary fibrosis is a progressive and deadly disorder with very few therapeutic options. Palomid 529 (8-(1-hydroxyethyl)-2-methoxy-3-(4-methoxybenzyloxy)-benzo[c]chromen-6-one; P529) is a novel dual inhibitor of mechanistic target of rapamycin complex 1/2 (mTORC1/2). In these studies, we investigated the effect of P529 on TGF-β-dependent signaling and myofibroblast differentiation. TGF-β-induced phosphorylation of the mTORC1 targets, p70 S6 kinase 1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), were both dose dependently inhibited by P529 in human lung fibroblasts with maximal inhibition occurring between 10-20 µM...
January 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28061838/cryptotanshinone-activates-ampk-tsc2-axis-leading-to-inhibition-of-mtorc1-signaling-in-cancer-cells
#15
Wenxing Chen, Yanhong Pan, Siliang Wang, Yuping Liu, Guangying Chen, Liang Zhou, Wenting Ni, Aiyun Wang, Yin Lu
BACKGROUND: Cryptotanshinone (CPT), a fat-soluble phenanthraquinone from Salvia miltiorrhiza Bunge, has been demonstrated to inhibit phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), a couple of direct downstream effectors of the mammalian target of rapamycin complex 1 (mTORC1), resulting in cancer cell arrested in G0 phase and subsequent inhibition of proliferation. However, its concrete molecular mechanism about how CPT inhibits mTORC1 signaling pathway is unclear...
January 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28036295/identification-of-mtor-as-a-primary-resistance-factor-of-the-iap-antagonist-at406-in-hepatocellular-carcinoma-cells
#16
Mao-Chuan Zhen, Fu-Qiang Wang, Shao-Feng Wu, Yi-Lin Zhao, Ping-Guo Liu, Zhen-Yu Yin
Dysregulation of inhibitor of apoptosis (IAP) proteins (IAPs) in hepatocellular carcinoma (HCC) is often associated with poor prognosis. Here we showed that AT406, an IAP antagonist, was cytotoxic and pro-apoptotic to both established (HepG2, SMMC-7721 lines) and primary HCC cells. Activation of mTOR could be a key resistance factor of AT406 in HCC cells. mTOR inhibition (by OSI-027), kinase-dead mutation or knockdown remarkably enhanced AT406-induced lethality in HCC cells. Reversely, forced-activation of mTOR by adding SC79 or exogenous expressing a constitutively active S6K1 (T389E) attenuated AT406-induced cytotoxicity against HCC cells...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28007963/interaction-of-p190a-rhogap-with-eif3a-and-other-translation-preinitiation-factors-suggests-a-role-in-protein-biosynthesis
#17
Prasanna Parasuraman, Peter Mulligan, James A Walker, Bihua Li, Myriam Boukhali, Wilhelm Haas, Andre Bernards
The negative regulator of Rho family GTPases, p190A RhoGAP, is one of six mammalian proteins harboring so-called FF motifs. To explore the function of these and other p190A segments, we identified interacting proteins by tandem mass spectrometry. Here we report that endogenous human p190A, but not its 50% identical p190B paralog, associates with all 13 eIF3 subunits and several other translational preinitiation factors. The interaction involves the first FF motif of p190A and the winged helix/PCI domain of eIF3A, is enhanced by serum stimulation and reduced by phosphatase treatment...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28004151/reciprocal-regulation-of-mtor-complexes-in-pancreatic-islets-from-humans-with-type-2-diabetes
#18
Ting Yuan, Sahar Rafizadeh, Kanaka Durga Devi Gorrepati, Blaz Lupse, Jose Oberholzer, Kathrin Maedler, Amin Ardestani
AIMS/HYPOTHESIS: Mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of nutritional status at the cellular and organismic level. While mTORC1 mediates beta cell growth and expansion, its hyperactivation has been observed in pancreatic islets from animal models of type 2 diabetes and leads to beta cell loss. We sought to determine whether such mTORC1 activation occurs in humans with type 2 diabetes or in metabolically stressed human islets and whether mTORC1 blockade can restore beta cell function of diabetic islets...
December 21, 2016: Diabetologia
https://www.readbyqxmd.com/read/27997905/blocking-mammalian-target-of-rapamycin-mtor-attenuates-hif-1%C3%AE-pathways-engaged-vascular-endothelial-growth-factor-vegf-in-diabetic-retinopathy
#19
Jie Wei, Hua Jiang, Hongrui Gao, Guangjie Wang
BACKGROUND/AIMS: Prior studies demonstrate that hypoxia inducible factor subtype 1α (HIF-1α) in retinal tissues is involved in development of diabetic retinopathy (DR). In this report, we particularly examined the role played by mammalian target of rapamycin (mTOR) in regulating expression of HIF-1α and its downstream pathway, namely vascular endothelial growth factor (VEGF). METHODS: Streptozotocin (STZ) was systemically injected to induce hyperglycemia in rats...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27993818/long-noncoding-rna-malat1-promotes-hepatocellular-carcinoma-development-by-srsf1-up-regulation-and-mtor-activation
#20
Pushkar Malakar, Asaf Shilo, Adi Mogilavsky, Ilan Stein, Eli Pikarsky, Yuval Nevo, Hadar Benyamini, Sharona Elgavish, Xinying Zong, Kannanganattu V Prasanth, Rotem Karni
Several long noncoding RNAs (lncRNA) are abrogated in cancer but their precise contributions to oncogenesis are still emerging. Here we report that the lncRNA MALAT1 is upregulated in hepatocellular carcinoma (HCC) and acts as a proto-oncogene through Wnt pathway activation and induction of the oncogenic splicing factor SRSF1. Induction of SRSF1 by MALAT1 modulates SRSF1 splicing targets, enhancing the production of anti-apoptotic splicing isoforms and activating the mTOR pathway by modulating the alternative splicing of S6K1...
December 19, 2016: Cancer Research
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