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10.1124/jpet.114.218099 http://scihub22266oqcxt.onion/10.1124/jpet.114.218099 C4201277!4201277 !25125579     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25125579 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Pharmacol+Exp+Ther 2014 ; 351 (2 ): 298-307 Nephropedia Template TP {{tp|p=25125579 |t=2014. Anaplerotic metabolism of alloreactive T cells provides a metabolic approach to treat graft-versus-host disease |pdf=|usr=}}{{25125579 }} gab.com Text Anaplerotic metabolism of alloreactive T cells provides a metabolic approach to treat graft-versus-host disease JO: J Pharmacol Exp Ther http://www.kidney.de/pget.php?&tw=1&pmid=25125579 #FOAvip T-cell activation requires increased ATP and biosynthesis to support proliferation and effector function. Most models of T-cell activation are based on in vitro culture systems and posit that aerobic glycolysis is employed to meet increased energetic and biosynthetic demands. By contrast, T cells activated in vivo by alloantigens in graft-versus-host disease (GVHD) increase mitochondrial oxygen consumption, fatty acid uptake, and oxidation, with small increases of glucose uptake and aerobic glycolysis. Here we show that these differences are not a consequence of alloactivation, because T cells activated in vitro either in a mixed lymphocyte reaction to the same alloantigens used in vivo or with agonistic anti-CD3/anti-CD28 antibodies increased aerobic glycolysis. Using targeted metabolic (13)C tracer fate associations, we elucidated the metabolic pathway(s) employed by alloreactive T cells in vivo that support this phenotype. We find that glutamine (Gln)-dependent tricarboxylic acid cycle anaplerosis is increased in alloreactive T cells and that Gln carbon contributes to ribose biosynthesis. Pharmacological modulation of oxidative phosphorylation rapidly reduces anaplerosis in alloreactive T cells and improves GVHD. On the basis of these data, we propose a model of T-cell metabolism that is relevant to activated lymphocytes in vivo, with implications for the discovery of new drugs for immune disorders. Twit Text FOAVip Anaplerotic metabolism of alloreactive T cells provides a metabolic approach to treat graft-versus-host disease ????J Pharmacol Exp Ther http://www.kidney.de/pget.php?&tw=1&pmid=25125579 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25125579 #FOAvip English Wikipedia <ref>{{Cite pmid|25125579 }}</ref> Anaplerotic metabolism of alloreactive T cells provides a metabolic approach to treat graft-versus-host disease #MMPMID25125579 Glick GD ; Rossignol R ; Lyssiotis CA ; Wahl D ; Lesch C ; Sanchez B ; Liu X ; Hao LY ; Taylor C ; Hurd A ; Ferrara JL ; Tkachev V ; Byersdorfer CA ; Boros L ; Opipari AW J Pharmacol Exp Ther 2014[Nov]; 351 (2 ): 298-307 PMID25125579 show ga T-cell activation requires increased ATP and biosynthesis to support proliferation and effector function. Most models of T-cell activation are based on in vitro culture systems and posit that aerobic glycolysis is employed to meet increased energetic and biosynthetic demands. By contrast, T cells activated in vivo by alloantigens in graft-versus-host disease (GVHD) increase mitochondrial oxygen consumption, fatty acid uptake, and oxidation, with small increases of glucose uptake and aerobic glycolysis. Here we show that these differences are not a consequence of alloactivation, because T cells activated in vitro either in a mixed lymphocyte reaction to the same alloantigens used in vivo or with agonistic anti-CD3/anti-CD28 antibodies increased aerobic glycolysis. Using targeted metabolic (13)C tracer fate associations, we elucidated the metabolic pathway(s) employed by alloreactive T cells in vivo that support this phenotype. We find that glutamine (Gln)-dependent tricarboxylic acid cycle anaplerosis is increased in alloreactive T cells and that Gln carbon contributes to ribose biosynthesis. Pharmacological modulation of oxidative phosphorylation rapidly reduces anaplerosis in alloreactive T cells and improves GVHD. On the basis of these data, we propose a model of T-cell metabolism that is relevant to activated lymphocytes in vivo, with implications for the discovery of new drugs for immune disorders. |Animals [MESH] |CD28 Antigens/immunology [MESH] |CD3 Complex/immunology [MESH] |Citric Acid Cycle/immunology [MESH] |Female [MESH] |Glutamine/metabolism [MESH] |Glycolysis/immunology [MESH] |Graft vs Host Disease/*immunology/metabolism [MESH] |Isoantigens/*immunology [MESH] |Lymphocyte Activation/*immunology [MESH] |Mice [MESH] |Oxidative Phosphorylation [MESH] |Ribose/biosynthesis [MESH]Anaplerotic metabolism of alloreactive T cells provides a metabolic ap(epmc).pdf DeepDyve Pubget Overpricing