The Experts below are selected from a list of 26109 Experts worldwide ranked by ideXlab platform

Akihiko Yoshimura - One of the best experts on this subject based on the ideXlab platform.

  • cyclic Adenosine Monophosphate suppresses the transcription of proinflammatory cytokines via the phosphorylated c fos protein
    Immunity, 2009
    Co-Authors: Keiko Koga, Giichi Takaesu, Ryoko Yoshida, Mako Nakaya, Takashi Kobayashi, Ichiko Kinjyo, Akihiko Yoshimura
    Abstract:

    Summary Intracellular cyclic Adenosine Monophosphate (cAMP) suppresses innate immunity by inhibiting proinflammatory cytokine production from monocytic cells. Enhanced expression of interleukin-10 (IL-10) has been suggested to be the mechanism of suppression. However, cAMP is still capable of suppressing production of the cytokines TNF-α and IL-12 in IL-10-deficient dendritic cells (DCs). Here, we demonstrated that the transcription factor c-Fos was responsible for the cAMP-mediated suppression of inflammatory cytokine production. c-Fos accumulated at high amounts in response to cAMP and lipopolysaccharide (LPS). Overexpression of c-Fos suppressed LPS-induced cytokine production, whereas cAMP-mediated suppression of TNF-α and IL-12 was impaired in Fos −/− DCs or in RAW264.7 cells treated with c-Fos siRNA. c-Fos physically interacted with p65 protein and reduced the recruitment of p65 to the Tnf promoter. Multiple sites of c-Fos were phosphorylated by the IKKβ protein. Thus, we propose that c-Fos is a substrate of IKKβ and is responsible for the immunosuppressive effect of cAMP.

  • cyclic Adenosine Monophosphate suppresses the transcription of proinflammatory cytokines via the phosphorylated c fos protein
    Immunity, 2009
    Co-Authors: Keiko Koga, Giichi Takaesu, Ryoko Yoshida, Mako Nakaya, Takashi Kobayashi, Ichiko Kinjyo, Akihiko Yoshimura
    Abstract:

    Intracellular cyclic Adenosine Monophosphate (cAMP) suppresses innate immunity by inhibiting proinflammatory cytokine production from monocytic cells. Enhanced expression of interleukin-10 (IL-10) has been suggested to be the mechanism of suppression. However, cAMP is still capable of suppressing production of the cytokines TNF-alpha and IL-12 in IL-10-deficient dendritic cells (DCs). Here, we demonstrated that the transcription factor c-Fos was responsible for the cAMP-mediated suppression of inflammatory cytokine production. c-Fos accumulated at high amounts in response to cAMP and lipopolysaccharide (LPS). Overexpression of c-Fos suppressed LPS-induced cytokine production, whereas cAMP-mediated suppression of TNF-alpha and IL-12 was impaired in Fos(-/-) DCs or in RAW264.7 cells treated with c-Fos siRNA. c-Fos physically interacted with p65 protein and reduced the recruitment of p65 to the Tnf promoter. Multiple sites of c-Fos were phosphorylated by the IKKbeta protein. Thus, we propose that c-Fos is a substrate of IKKbeta and is responsible for the immunosuppressive effect of cAMP.

Kathleen M Sakamoto - One of the best experts on this subject based on the ideXlab platform.

  • the function of cyclic Adenosine Monophosphate responsive element binding protein in hematologic malignancies
    Leukemia & Lymphoma, 2011
    Co-Authors: Bryan Mitton, Grace I Aldanamasangkay, Kathleen M Sakamoto
    Abstract:

    AbstractCentral to discovering novel approaches to treating leukemias and lymphomas is a clear understanding of the signaling networks which lead to unchecked cell cycle progression, proliferation, and survival. Cyclic-Adenosine Monophosphate (cAMP) responsive element-binding protein (CREB) represents a critical integrator of numerous signals from cytoplasmic kinase cascades, and is directly involved in controlling the transcription of genes critical for normal cellular proliferation and survival. Several lines of evidence implicate CREB as a proto-oncogene, as a number of translocations involving CREB and dysregulation of expression are both associated with oncogenesis. Thus, CREB represents a potential therapeutic target in leukemia. Here, we review CREB function and regulation in normal and aberrant hematopoiesis.

  • expression of cyclic Adenosine Monophosphate response element binding protein in acute leukemia
    Blood, 2002
    Co-Authors: Heather N Cransvargas, Elliot M Landaw, Smita Bhatia, George Sandusky, Theodore B Moore, Kathleen M Sakamoto
    Abstract:

    Cyclic Adenosine Monophosphate response-element binding protein (CREB) is a nuclear protein that regulates expression of genes that control cell proliferation, differentiation, and survival. To analyze CREB expression in leukemia cells, we conducted Western blot analysis of bone marrow cells obtained from patients with acute lymphoblastic leukemia, patients with acute myeloid leukemia, and patients without active leukemia. CREB was expressed at a higher frequency in bone marrow cells from patients with acute lymphoid or myeloid leukemia than in patients with leukemia remission or without leukemia. Our results indicate that CREB expression could be a useful marker for leukemia in patients with acute disease and suggest a role for CREB in leukemogenesis.

Hiroaki Nomori - One of the best experts on this subject based on the ideXlab platform.

Laurie J Goodyear - One of the best experts on this subject based on the ideXlab platform.

  • 5 Adenosine Monophosphate activated protein kinase metabolism and exercise
    Sports Medicine, 2004
    Co-Authors: William G Aschenbach, Kei Sakamoto, Laurie J Goodyear
    Abstract:

    The 5' Adenosine Monophosphate-activated protein kinase (AMPK) is a member of a metabolite-sensing protein kinase family that functions as a metabolic 'fuel gauge' in skeletal muscle. AMPK is a ubiquitous heterotrimeric protein, consisting of an alpha catalytic, and beta and gamma regulatory subunits that exist in multiple isoforms and are all required for full enzymatic activity. During exercise, AMPK becomes activated in skeletal muscle in response to changes in cellular energy status (e.g. increased Adenosine Monophosphate [AMP]/Adenosine triphosphate [ATP] and creatine/phosphocreatine ratios) in an intensity-dependent manner, and serves to inhibit ATP-consuming pathways, and activate pathways involved in carbohydrate and fatty-acid metabolism to restore ATP levels. Recent evidence shows that although AMPK plays this key metabolic role during acute bouts of exercise, it is also an important component of the adaptive response of skeletal muscles to endurance exercise training because of its ability to alter muscle fuel reserves and expression of several exercise-responsive genes. This review discusses the putative roles of AMPK in acute and chronic exercise responses, and suggests avenues for future AMPK research in exercise physiology and biochemistry.

  • increased Adenosine Monophosphate activated protein kinase activity in rat hearts with pressure overload hypertrophy
    Circulation, 2001
    Co-Authors: Rong Tian, Nicolas Musi, Jessica Dagostino, Michael F Hirshman, Laurie J Goodyear
    Abstract:

    Background Recent reports suggest that activation of Adenosine Monophosphate (AMP)–activated protein kinase (AMPK), in response to acute changes in cellular energy status in cardiac and skeletal muscles, results in altered substrate utilization. We hypothesized that chronic alterations in myocardial energetics in hypertrophied hearts (left ventricular hypertrophy, LVH) will lead to elevated AMPK activity, which in turn regulates substrate utilization. Methods and Results Using 31P NMR spectroscopy and biochemical assays, we found that in LVH hearts, Adenosine triphosphate (ATP) concentration decreased by 10%, phosphocreatine concentration decreased by 30%, and total creatine concentration was unchanged. Thus, the ratio of phosphocreatine/creatine decreased to one third of controls, and the ratio of AMP/ATP increased to 5 times above controls. These changes were associated with increased α1 and α2 AMPK activity (3.5- and 4.8-fold above controls, respectively). The increase in AMPK α1 activity was accompani...

Mario D Cordero - One of the best experts on this subject based on the ideXlab platform.

  • Adenosine Monophosphate amp activated protein kinase a new target for nutraceutical compounds
    International Journal of Molecular Sciences, 2017
    Co-Authors: Fabiola Marinaguilar, Luis E Pavillard, Francesca Giampieri, Pedro Bullon, Mario D Cordero
    Abstract:

    Adenosine Monophosphate-activated protein kinase (AMPK) is an important energy sensor which is activated by increases in Adenosine Monophosphate (AMP)/Adenosine triphosphate (ATP) ratio and/or Adenosine diphosphate (ADP)/ATP ratio, and increases different metabolic pathways such as fatty acid oxidation, glucose transport and mitochondrial biogenesis. In this sense, AMPK maintains cellular energy homeostasis by induction of catabolism and inhibition of ATP-consuming biosynthetic pathways to preserve ATP levels. Several studies indicate a reduction of AMPK sensitivity to cellular stress during aging and this could impair the downstream signaling and the maintenance of the cellular energy balance and the stress resistance. However, several diseases have been related with an AMPK dysfunction. Alterations in AMPK signaling decrease mitochondrial biogenesis, increase cellular stress and induce inflammation, which are typical events of the aging process and have been associated to several pathological processes. In this sense, in the last few years AMPK has been identified as a very interesting target and different nutraceutical compounds are being studied for an interesting potential effect on AMPK induction. In this review, we will evaluate the interaction of the different nutraceutical compounds to induce the AMPK phosphorylation and the applications in diseases such as cancer, type II diabetes, neurodegenerative diseases or cardiovascular diseases.