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10.1089/ars.2014.6025 http://scihub22266oqcxt.onion/10.1089/ars.2014.6025 C4657521!4657521!25353619     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Antioxid+Redox+Signal 2015 ; 23 (14): 1092-105 Nephropedia Template TP {{tp|p=25353619|t=2015. Targeting of Gamma-Glutamyl-Cysteine Ligase by miR-433 Reduces Glutathione Biosynthesis and Promotes TGF-?-Dependent Fibrogenesis |pdf=|usr=}}{{25353619}} gab.com Text Targeting of Gamma-Glutamyl-Cysteine Ligase by miR-433 Reduces Glutathione Biosynthesis and Promotes TGF- -Dependent Fibrogenesis JO: Antioxid Redox Signal http://www.kidney.de/pget.php?&tw=1&pmid=25353619 #FOAvip Aims: Glutathione (GSH) is the main antioxidant against cell damage. Several pathological states course with reduced nucleophilic tone and perturbation of redox homeostasis due to changes in the 2GSH/GSSG ratio. Here, we investigated the regulation of the rate-limiting GSH biosynthetic heterodimeric enzyme ?-glutamyl-cysteine ligase (GCL) by microRNAs (miRNAs). Results: ?In silico? analysis of the 3?- untranslated regions (UTRs) of both catalytic (GCLc) and regulatory (GCLm) subunits of GCL enabled an identification of miR-433 as a strong candidate for the targeting of GCL. Transitory overexpression of miR-433 in human umbilical vein endothelial cells (HUVEC) showed a downregulation of both GCLc and GCLm in a nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-independent manner. Increases in pro-oxidant stimuli such as exposure to hydrogen peroxide or GSH depletion in endothelial and hepatic cells caused an expected increase in GCLc and GCLm protein expression and abrogation of miR-433 levels, thus supporting a cross-regulation of these pathways. Treatment of HUVEC with miR-433 resulted in reduced antioxidant and redox potentials, increased S-glutathionylation, and reduced endothelial nitric oxide synthase activation. In vivo models of renal and hepatic fibrosis were associated with transforming growth factor ?1 (TGF-?1)-related reduction of GCLc and GCLm levels that were miR-433 dependent. Innovation and Conclusion: We describe for the first time an miRNA, miR-433, capable of directly targeting GCL and promoting functional consequences in endothelial physiology and fibrotic processes by decreasing GSH levels. Antioxid. Redox Signal. 23, 1092?1105. Twit Text FOAVip Targeting of Gamma-Glutamyl-Cysteine Ligase by miR-433 Reduces Glutathione Biosynthesis and Promotes TGF- -Dependent Fibrogenesis ????Antioxid Redox Signal http://www.kidney.de/pget.php?&tw=1&pmid=25353619 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25353619 #FOAvip English Wikipedia <ref>{{Cite pmid|25353619}}</ref> Targeting of Gamma-Glutamyl-Cysteine Ligase by miR-433 Reduces Glutathione Biosynthesis and Promotes TGF-?-Dependent Fibrogenesis #MMPMID25353619 Espinosa-Diez C; Fierro-Fernández M; Sánchez-Gómez F; Rodríguez-Pascual F; Alique M; Ruiz-Ortega M; Beraza N; Martínez-Chantar ML; Fernández-Hernando C; Lamas S Antioxid Redox Signal 2015[Nov]; 23 (14): 1092-105 PMID25353619show ga Aims: Glutathione (GSH) is the main antioxidant against cell damage. Several pathological states course with reduced nucleophilic tone and perturbation of redox homeostasis due to changes in the 2GSH/GSSG ratio. Here, we investigated the regulation of the rate-limiting GSH biosynthetic heterodimeric enzyme ?-glutamyl-cysteine ligase (GCL) by microRNAs (miRNAs). Results: ?In silico? analysis of the 3?- untranslated regions (UTRs) of both catalytic (GCLc) and regulatory (GCLm) subunits of GCL enabled an identification of miR-433 as a strong candidate for the targeting of GCL. Transitory overexpression of miR-433 in human umbilical vein endothelial cells (HUVEC) showed a downregulation of both GCLc and GCLm in a nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-independent manner. Increases in pro-oxidant stimuli such as exposure to hydrogen peroxide or GSH depletion in endothelial and hepatic cells caused an expected increase in GCLc and GCLm protein expression and abrogation of miR-433 levels, thus supporting a cross-regulation of these pathways. Treatment of HUVEC with miR-433 resulted in reduced antioxidant and redox potentials, increased S-glutathionylation, and reduced endothelial nitric oxide synthase activation. In vivo models of renal and hepatic fibrosis were associated with transforming growth factor ?1 (TGF-?1)-related reduction of GCLc and GCLm levels that were miR-433 dependent. Innovation and Conclusion: We describe for the first time an miRNA, miR-433, capable of directly targeting GCL and promoting functional consequences in endothelial physiology and fibrotic processes by decreasing GSH levels. Antioxid. Redox Signal. 23, 1092?1105. äTargeting of Gamma-Glutamyl-Cysteine Ligase by miR-433 Reduces Glutath(epmc).pdf DeepDyve Pubget Overpricing