関: 70-kDa ribosomal protein S6 kinase、p70S6K

WordNet

the 19th letter of the Roman alphabet (同)s
an enzyme that catalyzes the conversion of a proenzyme to an active enzyme
the basic unit of money in Papua New Guinea

PrepTutorEJDIC

sulfurの化学記号 / {略}South[ern]

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1. インスリン様成長因子Iの生理学 physiology of insulin like growth factor 1
2. 移植免疫 transplantation immunobiology

English Journal

Deficiency of OSMRβ Exacerbates High-Fat Diet-Induced Obesity and Related Metabolic Disorders in Mice.

Komori T1, Tanaka M, Senba E, Miyajima A, Morikawa Y.Author information 1Wakayama Medical University, Japan;AbstractOncostatin M (OSM) belongs to the IL-6 family of cytokines and has diverse biological effects, including the modulation of inflammatory responses. In the present study, we analyzed the roles of OSM signaling in obesity and related metabolic disorders. Under a high-fat diet (HFD) condition, OSM receptor β subunit-deficient (OSMRβ-/-) mice exhibited increases in body weight and food intake compared to those observed in WT mice. In addition, adipose tissue inflammation, insulin resistance, and hepatic steatosis were more severe in OSMRβ-/- mice than in wild-type (WT) mice. These metabolic phenotypes did not improve when OSMRβ-/- mice were pair-fed with WT mice, suggesting that the effects of OSM signaling on these phenotypes are independent of the increases in the body weight and food intake. In the liver of OSMRβ-/- mice, the insulin-induced phosphorylation of p70 S6 kinase remained intact, while insulin-induced FOXO1 phosphorylation was impaired. In addition, OSMRβ-/- mice displayed a higher expression of genes related to de novo lipogenesis in the liver than WT mice. Furthermore, treatment of genetically obese ob/ob mice with OSM improved insulin resistance, adipose tissue inflammation, and hepatic steatosis. Intraportal administration of OSM into ob/ob mice activated STAT3 and increased the expression of long-chain acyl-CoA synthetase (ACSL) 3 and ACSL5 with decreased expression of fatty acid synthase in the liver, suggesting that OSM directly induces lipolysis and suppresses lipogenesis in the liver of obese mice. These findings suggest that defects in OSM signaling promote the deterioration of HFD-induced obesity and related metabolic disorders.
The Journal of biological chemistry.J Biol Chem.2014 Apr 2. [Epub ahead of print]
Oncostatin M (OSM) belongs to the IL-6 family of cytokines and has diverse biological effects, including the modulation of inflammatory responses. In the present study, we analyzed the roles of OSM signaling in obesity and related metabolic disorders. Under a high-fat diet (HFD) condition, OSM recep
PMID 24695736

Characterization of pomiferin triacetate as a novel mTOR and translation inhibitor.

Bajer MM1, Kunze MM1, Blees JS1, Bokesch HR2, Chen H3, Brauß TF1, Dong Z3, Gustafson KR4, Biondi RM5, Henrich CJ2, McMahon JB4, Colburn NH6, Schmid T7, Brüne B1.Author information 1Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.2Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702, USA; Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.3The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.4Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702, USA.5Research Group PhosphoSites, Department of Internal Medicine I, University Clinic, 60590 Frankfurt, Germany.6Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702, USA.7Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany. Electronic address: t.schmid@biochem.uni-frankfurt.de.AbstractDeregulation of the phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR)-70kDa ribosomal protein S6 kinase 1 (p70(S6K)) pathway is commonly observed in many tumors. This pathway controls proliferation, survival, and translation, and its overactivation is associated with poor prognosis for tumor-associated survival. Current efforts focus on the development of novel inhibitors of this pathway. In a cell-based high-throughput screening assay of 15,272 pure natural compounds, we identified pomiferin triacetate as a potent stabilizer of the tumor suppressor programmed cell death 4 (Pdcd4). Mechanistically, pomiferin triacetate appeared as a general inhibitor of the PI3K-Akt-mTOR-p70(S6K) cascade. Interference with this pathway occurred downstream of Akt but upstream of p70(S6K). Specifically, mTOR kinase emerged as the molecular target of pomiferin triacetate, with similar activities against mTOR complexes 1 and 2. In an in vitro mTOR kinase assay pomiferin triacetate dose-dependently inhibited mTOR with an IC50 of 6.2μM. Molecular docking studies supported the interaction of the inhibitor with the catalytic site of mTOR. Importantly, pomiferin triacetate appeared to be highly selective for mTOR compared to a panel of 17 lipid and 50 protein kinases tested. As a consequence of the mTOR inhibition, pomiferin triacetate efficiently attenuated translation. In summary, pomiferin triacetate emerged as a novel and highly specific mTOR inhibitor with strong translation inhibitory effects. Thus, it might be an interesting lead structure for the development of mTOR- and translation-targeted anti-tumor therapies.
Biochemical pharmacology.Biochem Pharmacol.2014 Apr 1;88(3):313-21. doi: 10.1016/j.bcp.2014.01.034. Epub 2014 Feb 7.
Deregulation of the phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR)-70kDa ribosomal protein S6 kinase 1 (p70(S6K)) pathway is commonly observed in many tumors. This pathway controls proliferation, survival, and translation, and its overactivation is associated with poor
PMID 24513322

Effects of Physical Exercise on the P38MAPK/REDD1/14-3-3 Pathways in the Myocardium of Diet-Induced Obesity Rats.

Pieri BL1, Souza DR1, Luciano TF1, Marques SO1, Pauli JR2, Silva AS3, Ropelle ER2, Pinho RA1, Lira FS4, De Souza CT1.Author information 1Laboratory of Exercise Biochemistry and Physiology, Health Sciences Unit, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.2Faculty of Applied Sciences, University of Campinas - UNICAMP, Limeira, São Paulo, Brazil.3School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.4Immunometabolism Research Group, Department of Physical Education, Universidade Estadual Paulista, UNESP, Presidente Prudente, São Paulo, Brazil.AbstractObesity is associated with myocardial insulin resistance and impairment of the mammalian target of rapamycin (mTOR) signaling pathway. The activation of the mTOR cascade by exercise has been largely shown in skeletal muscle, but insufficiently analyzed in myocardial tissue. In addition, little is known regarding the mTOR upstream molecules in the hearts of obese animals and even less about the role of exercise in this process. Thus, the present study was aimed to evaluate the effects of physical exercise on P38 Mitogen-Activated Protein Kinase (P38MAPK) phosphorylation and the REDD1 (regulated in development and DNA damage responses 1) and 14-3-3 protein levels in the myocardium of diet-induced obesity (DIO) rats. After achievement of DIO and insulin resistance, Wistar rats were divided in 2 groups: sedentary obese rats and obese rats performed treadmill running (50-min/day, 5 days per week velocity of 1.0 km/h for 2 months). Forty-eight hours after the final physical exercise, the rats were killed, and the myocardial tissue was removed for Western blot analysis. DIO increased the REDD1 protein levels and reduced the 14-3-3 protein levels and P38MAPK, mTOR, P70S6k (p70 ribosomal S6 protein kinase), and 4EBP1 (4E-binding protein-1) phosphorylation. Interestingly, physical exercise reduced the REDD1 protein levels and increased the 14-3-3 protein levels and P38MAPK, mTOR, P70S6k, and 4EBP1 phosphorylation. Moreover, exercise increased the REDD1/14-3-3 association in the heart. Our results indicate that the phospho-P38MAPK, REDD1, and 14-3-3 protein levels were reduced in the myocardium of obese rats and that physical exercise increased the protein levels of these molecules.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.Horm Metab Res.2014 Apr 1. [Epub ahead of print]
Obesity is associated with myocardial insulin resistance and impairment of the mammalian target of rapamycin (mTOR) signaling pathway. The activation of the mTOR cascade by exercise has been largely shown in skeletal muscle, but insufficiently analyzed in myocardial tissue. In addition, little is kn
PMID 24691733

Japanese Journal

Aglycon of Rhizochalin from the Rhizochalina incrustata Induces Apoptosis via Activation of AMP-Activated Protein Kinase in HT-29 Colon Cancer Cells

Khanal Prem,Kang Bong Seok,Yun Hyo Jeong,Cho Hae-Guk,Makarieva Tatyana Nikolaevna,Choi Hong Seok
Biological & Pharmaceutical Bulletin 34(10), 1553-1558, 2011
… Here, we demonstrate that aglycon of rhizochalin (AglRhz) from the Rhizochalina incrustata induces AMP-activated protein kinase (AMPK) phosphorylation, and thereby inhibits mammalian target of rapamycin (mTOR)-p70S6 kinase-extracellular signal-regulated kinase (ERK) signaling and activator protein 1 (AP-1) activity via phosphorylation of Raptor in HT-29 cells. …
NAID 130001086586

Overexpression of the Lily p70^<s6k> Gene in Arabidopsis Affects Elongation of Flower Organs and Indicates TOR-Dependent Regulation of AP3, PI and SUP Translation