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10.1074/jbc.M116.738591 http://scihub22266oqcxt.onion/10.1074/jbc.M116.738591 C5095399!5095399 !27621313     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 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 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 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27621313 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Biol+Chem 2016 ; 291 (45 ): 23428-23439 Nephropedia Template TP {{tp|p=27621313 |t=2016. Physiological Expression of AMPK?2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice |pdf=|usr=}}{{27621313 }} gab.com Text Physiological Expression of AMPK 2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=27621313 #FOAvip Mutations of the AMP-activated kinase gamma 2 subunit (AMPK?2), N488I (AMPK?2(NI)) and R531G (AMPK?2(RG)), are associated with Wolff-Parkinson-White (WPW) syndrome, a cardiac disorder characterized by ventricular pre-excitation in humans. Cardiac-specific transgenic overexpression of human AMPK?2(NI) or AMPK?2(RG) leads to constitutive AMPK activation and the WPW phenotype in mice. However, overexpression of these mutant proteins also caused profound, non-physiological increase in cardiac glycogen, which might abnormally alter the true phenotype. To investigate whether physiological levels of AMPK?2(NI) or AMPK?2(RG) mutation cause WPW syndrome and metabolic changes in other organs, we generated two knock-in mouse lines on the C57BL/6N background harboring mutations of human AMPK?2(NI) and AMPK?2(RG), respectively. Similar to the reported phenotypes of mice overexpressing AMPK?2(NI) or AMPK?2(RG) in the heart, both lines developed WPW syndrome and cardiac hypertrophy; however, these effects were independent of cardiac glycogen accumulation. Compared with AMPK?2(WT) mice, AMPK?2(NI) and AMPK?2(RG) mice exhibited reduced body weight, fat mass, and liver steatosis when fed with a high fat diet (HFD). Surprisingly, AMPK?2(RG) but not AMPK?2(NI) mice fed with an HFD exhibited severe kidney injury characterized by glycogen accumulation, inflammation, apoptosis, cyst formation, and impaired renal function. These results demonstrate that expression of AMPK?2(NI) and AMPK?2(RG) mutations at physiological levels can induce beneficial metabolic effects but that this is accompanied by WPW syndrome. Our data also reveal an unexpected effect of AMPK?2(RG) in the kidney, linking lifelong constitutive activation of AMPK to a potential risk for kidney dysfunction in the context of an HFD. Twit Text FOAVip Physiological Expression of AMPK 2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=27621313 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27621313 #FOAvip English Wikipedia <ref>{{Cite pmid|27621313 }}</ref> Physiological Expression of AMPK?2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice #MMPMID27621313 Yang X ; Mudgett J ; Bou-About G ; Champy MF ; Jacobs H ; Monassier L ; Pavlovic G ; Sorg T ; Herault Y ; Petit-Demoulière B ; Lu K ; Feng W ; Wang H ; Ma LJ ; Askew R ; Erion MD ; Kelley DE ; Myers RW ; Li C ; Guan HP J Biol Chem 2016[Nov]; 291 (45 ): 23428-23439 PMID27621313 show ga Mutations of the AMP-activated kinase gamma 2 subunit (AMPK?2), N488I (AMPK?2(NI)) and R531G (AMPK?2(RG)), are associated with Wolff-Parkinson-White (WPW) syndrome, a cardiac disorder characterized by ventricular pre-excitation in humans. Cardiac-specific transgenic overexpression of human AMPK?2(NI) or AMPK?2(RG) leads to constitutive AMPK activation and the WPW phenotype in mice. However, overexpression of these mutant proteins also caused profound, non-physiological increase in cardiac glycogen, which might abnormally alter the true phenotype. To investigate whether physiological levels of AMPK?2(NI) or AMPK?2(RG) mutation cause WPW syndrome and metabolic changes in other organs, we generated two knock-in mouse lines on the C57BL/6N background harboring mutations of human AMPK?2(NI) and AMPK?2(RG), respectively. Similar to the reported phenotypes of mice overexpressing AMPK?2(NI) or AMPK?2(RG) in the heart, both lines developed WPW syndrome and cardiac hypertrophy; however, these effects were independent of cardiac glycogen accumulation. Compared with AMPK?2(WT) mice, AMPK?2(NI) and AMPK?2(RG) mice exhibited reduced body weight, fat mass, and liver steatosis when fed with a high fat diet (HFD). Surprisingly, AMPK?2(RG) but not AMPK?2(NI) mice fed with an HFD exhibited severe kidney injury characterized by glycogen accumulation, inflammation, apoptosis, cyst formation, and impaired renal function. These results demonstrate that expression of AMPK?2(NI) and AMPK?2(RG) mutations at physiological levels can induce beneficial metabolic effects but that this is accompanied by WPW syndrome. Our data also reveal an unexpected effect of AMPK?2(RG) in the kidney, linking lifelong constitutive activation of AMPK to a potential risk for kidney dysfunction in the context of an HFD. |*Mutation [MESH] |AMP-Activated Protein Kinases/*genetics [MESH] |Animals [MESH] |Apoptosis [MESH] |Disease Models, Animal [MESH] |Gene Knock-In Techniques [MESH] |Inflammation/genetics/pathology [MESH] |Kidney/metabolism/pathology [MESH] |Male [MESH] |Mice, Inbred C57BL [MESH] |Renal Insufficiency/*genetics/pathology [MESH]Physiological Expression of AMPK?2RG Mutation Causes Wolff-Parkinson-W(epmc).pdf DeepDyve Pubget Overpricing