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10.1161/ATVBAHA.113.302200 http://scihub22266oqcxt.onion/10.1161/ATVBAHA.113.302200 24158513!ä!24158513 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 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\24158513.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Arterioscler+Thromb+Vasc+Biol 2014 ; 34 (1): 81-9 Nephropedia Template TP {{tp|p=24158513|t=2014. Globotriaosylceramide induces lysosomal degradation of endothelial KCa3 1 in fabry disease |pdf=|usr=}}{{24158513}} gab.com Text Globotriaosylceramide induces lysosomal degradation of endothelial KCa3 1 in fabry disease JO: Arterioscler Thromb Vasc Biol http://www.kidney.de/pget.php?&tw=1&pmid=24158513 #FOAvip OBJECTIVE: Globotriaosylceramide (Gb3) induces KCa3.1 downregulation in Fabry disease (FD). We investigated whether Gb3 induces KCa3.1 endocytosis and degradation. APPROACH AND RESULTS: KCa3.1, especially plasma membrane-localized KCa3.1, was downregulated in both Gb3-treated mouse aortic endothelial cells (MAECs) and human umbilical vein endothelial cells. Gb3-induced KCa3.1 downregulation was prevented by lysosomal inhibitors but not by a proteosomal inhibitor. Endoplasmic reticulum stress-inducing agents did not induce KCa3.1 downregulation. Gb3 upregulated the protein levels of early endosome antigen 1 and lysosomal-associated membrane protein 2 in MAECs. Compared with MAECs from age-matched wild-type mice, those from aged alpha-galactosidase A (Gla)-knockout mice, an animal model of FD, showed downregulated KCa3.1 expression and upregulated early endosome antigen 1 and lysosomal-associated membrane protein 2 expression. In contrast, no significant difference was found in early endosome antigen 1 and lysosomal-associated membrane protein 2 expression between young Gla-knockout and wild-type MAECs. In aged Gla-knockout MAECs, clathrin was translocated close to the cell border and clathrin knockdown recovered KCa3.1 expression. Rab5, an effector of early endosome antigen 1, was upregulated, and Rab5 knockdown restored KCa3.1 expression, the current, and endothelium-dependent relaxation. CONCLUSIONS: -Gb3 accelerates the endocytosis and lysosomal degradation of endothelial KCa3.1 via a clathrin-dependent process, leading to endothelial dysfunction in FD. Twit Text FOAVip Globotriaosylceramide induces lysosomal degradation of endothelial KCa3 1 in fabry disease ????Arterioscler Thromb Vasc Biol http://www.kidney.de/pget.php?&tw=1&pmid=24158513 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24158513 #FOAvip English Wikipedia <ref>{{Cite pmid|24158513}}</ref> Globotriaosylceramide induces lysosomal degradation of endothelial KCa3 1 in fabry disease #MMPMID24158513 Choi S; Kim JA; Na HY; Cho SE; Park S; Jung SC; Suh SH Arterioscler Thromb Vasc Biol 2014[Jan]; 34 (1): 81-9 PMID24158513show ga OBJECTIVE: Globotriaosylceramide (Gb3) induces KCa3.1 downregulation in Fabry disease (FD). We investigated whether Gb3 induces KCa3.1 endocytosis and degradation. APPROACH AND RESULTS: KCa3.1, especially plasma membrane-localized KCa3.1, was downregulated in both Gb3-treated mouse aortic endothelial cells (MAECs) and human umbilical vein endothelial cells. Gb3-induced KCa3.1 downregulation was prevented by lysosomal inhibitors but not by a proteosomal inhibitor. Endoplasmic reticulum stress-inducing agents did not induce KCa3.1 downregulation. Gb3 upregulated the protein levels of early endosome antigen 1 and lysosomal-associated membrane protein 2 in MAECs. Compared with MAECs from age-matched wild-type mice, those from aged alpha-galactosidase A (Gla)-knockout mice, an animal model of FD, showed downregulated KCa3.1 expression and upregulated early endosome antigen 1 and lysosomal-associated membrane protein 2 expression. In contrast, no significant difference was found in early endosome antigen 1 and lysosomal-associated membrane protein 2 expression between young Gla-knockout and wild-type MAECs. In aged Gla-knockout MAECs, clathrin was translocated close to the cell border and clathrin knockdown recovered KCa3.1 expression. Rab5, an effector of early endosome antigen 1, was upregulated, and Rab5 knockdown restored KCa3.1 expression, the current, and endothelium-dependent relaxation. CONCLUSIONS: -Gb3 accelerates the endocytosis and lysosomal degradation of endothelial KCa3.1 via a clathrin-dependent process, leading to endothelial dysfunction in FD. |Animals[MESH] |Cells, Cultured[MESH] |Clathrin/genetics/metabolism[MESH] |Disease Models, Animal[MESH] |Endocytosis[MESH] |Endothelial Cells/*enzymology[MESH] |Endothelium, Vascular/*enzymology/physiopathology[MESH] |Fabry Disease/*enzymology/genetics/physiopathology[MESH] |Human Umbilical Vein Endothelial Cells/enzymology[MESH] |Humans[MESH] |Intermediate-Conductance Calcium-Activated Potassium Channels/*metabolism[MESH] |Lysosomal-Associated Membrane Protein 2/metabolism[MESH] |Lysosomes/*metabolism[MESH] |Mice[MESH] |Mice, Knockout[MESH] |Protein Transport[MESH] |Proteolysis[MESH] |RNA Interference[MESH] |Transfection[MESH] |Trihexosylceramides/*metabolism[MESH] |Vasodilation[MESH] |Vesicular Transport Proteins/metabolism[MESH] |alpha-Galactosidase/genetics/metabolism[MESH]Globotriaosylceramide induces lysosomal degradation of endothelial KCa(epmc).pdf DeepDyve Pubget Overpricing