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10.1038/mt.2015.224 http://scihub22266oqcxt.onion/10.1038/mt.2015.224 C4886931!4886931!26689264     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Mol+Ther 2016 ; 24 (4): 719-25 Nephropedia Template TP {{tp|p=26689264|t=2016. Glycolate Oxidase Is a Safe and Efficient Target for Substrate Reduction Therapy in a Mouse Model of Primary Hyperoxaluria Type I |pdf=|usr=}}{{26689264}} gab.com Text Glycolate Oxidase Is a Safe and Efficient Target for Substrate Reduction Therapy in a Mouse Model of Primary Hyperoxaluria Type I JO: Mol Ther http://www.kidney.de/pget.php?&tw=1&pmid=26689264 #FOAvip Primary hyperoxaluria type 1 (PH1) is caused by deficient alanine-glyoxylate aminotransferase, the human peroxisomal enzyme that detoxifies glyoxylate. Glycolate is one of the best-known substrates leading to glyoxylate production, via peroxisomal glycolate oxidase (GO). Using genetically modified mice, we herein report GO as a safe and efficient target for substrate reduction therapy (SRT) in PH1. We first generated a GO-deficient mouse (Hao1?/?) that presented high urine glycolate levels but no additional phenotype. Next, we produced double KO mice (Agxt1?/?Hao1?/?) that showed low levels of oxalate excretion compared with hyperoxaluric mice model (Agxt1?/?). Previous studies have identified some GO inhibitors, such as 4-carboxy-5-[(4-chlorophenyl)sulfanyl]-1,2,3-thiadiazole (CCPST). We herein report that CCPST inhibits GO in Agxt1?/? hepatocytes and significantly reduces their oxalate production, starting at 25 µM. We also tested the ability of orally administered CCPST to reduce oxalate excretion in Agxt1?/? mice, showing that 30?50% reduction in urine oxalate can be achieved. In summary, we present proof-of-concept evidence for SRT in PH1. These encouraging results should be followed by a medicinal chemistry programme that might yield more potent GO inhibitors and eventually could result in a pharmacological treatment for this rare and severe inborn error of metabolism. Twit Text FOAVip Glycolate Oxidase Is a Safe and Efficient Target for Substrate Reduction Therapy in a Mouse Model of Primary Hyperoxaluria Type I ????Mol Ther http://www.kidney.de/pget.php?&tw=1&pmid=26689264 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26689264 #FOAvip English Wikipedia <ref>{{Cite pmid|26689264}}</ref> Glycolate Oxidase Is a Safe and Efficient Target for Substrate Reduction Therapy in a Mouse Model of Primary Hyperoxaluria Type I #MMPMID26689264 Martin-Higueras C; Luis-Lima S; Salido E Mol Ther 2016[Apr]; 24 (4): 719-25 PMID26689264show ga Primary hyperoxaluria type 1 (PH1) is caused by deficient alanine-glyoxylate aminotransferase, the human peroxisomal enzyme that detoxifies glyoxylate. Glycolate is one of the best-known substrates leading to glyoxylate production, via peroxisomal glycolate oxidase (GO). Using genetically modified mice, we herein report GO as a safe and efficient target for substrate reduction therapy (SRT) in PH1. We first generated a GO-deficient mouse (Hao1?/?) that presented high urine glycolate levels but no additional phenotype. Next, we produced double KO mice (Agxt1?/?Hao1?/?) that showed low levels of oxalate excretion compared with hyperoxaluric mice model (Agxt1?/?). Previous studies have identified some GO inhibitors, such as 4-carboxy-5-[(4-chlorophenyl)sulfanyl]-1,2,3-thiadiazole (CCPST). We herein report that CCPST inhibits GO in Agxt1?/? hepatocytes and significantly reduces their oxalate production, starting at 25 µM. We also tested the ability of orally administered CCPST to reduce oxalate excretion in Agxt1?/? mice, showing that 30?50% reduction in urine oxalate can be achieved. In summary, we present proof-of-concept evidence for SRT in PH1. These encouraging results should be followed by a medicinal chemistry programme that might yield more potent GO inhibitors and eventually could result in a pharmacological treatment for this rare and severe inborn error of metabolism. äGlycolate Oxidase Is a Safe and Efficient Target for Substrate Reducti(epmc).pdf DeepDyve Pubget Overpricing