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10.1152/ajprenal.00216.2019 http://scihub22266oqcxt.onion/10.1152/ajprenal.00216.2019 31364380!6843039!31364380     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 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Am+J+Physiol+Renal+Physiol 2019 ; 317 (4): F825-F838 Nephropedia Template TP {{tp|p=31364380|t=2019. Mg(2+) restriction downregulates NCC through NEDD4-2 and prevents its activation by hypokalemia |pdf=|usr=}}{{31364380}} gab.com Text Mg(2+) restriction downregulates NCC through NEDD4-2 and prevents its activation by hypokalemia JO: Am J Physiol Renal Physiol http://www.kidney.de/pget.php?&tw=1&pmid=31364380 #FOAvip Hypomagnesemia is associated with reduced kidney function and life-threatening complications and sustains hypokalemia. The distal convoluted tubule (DCT) determines final urinary Mg(2+) excretion and, via activity of the Na(+)-Cl(-) cotransporter (NCC), also plays a key role in K(+) homeostasis by metering Na(+) delivery to distal segments. Little is known about the mechanisms by which plasma Mg(2+) concentration regulates NCC activity and how low-plasma Mg(2+) concentration and K(+) concentration interact to modulate NCC activity. To address this, we performed dietary manipulation studies in mice. Compared with normal diet, abundances of total NCC and phosphorylated NCC (pNCC) were lower after short-term (3 days) or long-term (14 days) dietary Mg(2+) restriction. Altered NCC activation is unlikely to play a role, since we also observed lower total NCC abundance in mice lacking the two NCC-activating kinases, STE20/SPS-1-related proline/alanine-rich kinase and oxidative stress response kinase-1, after Mg(2+) restriction. The E3 ubiquitin-protein ligase NEDD4-2 regulates NCC abundance during dietary NaCl loading or K(+) restriction. Mg(2+) restriction did not lower total NCC abundance in inducible nephron-specific neuronal precursor cell developmentally downregulated 4-2 (NEDD4-2) knockout mice. Total NCC and pNCC abundances were similar after short-term Mg(2+) or combined Mg(2+)-K(+) restriction but were dramatically lower compared with a low-K(+) diet. Therefore, sustained NCC downregulation may serve a mechanism that enhances distal Na(+) delivery during states of hypomagnesemia, maintaining hypokalemia. Similar results were obtained with long-term Mg(2+)-K(+) restriction, but, surprisingly, NCC was not activated after long-term K(+) restriction despite lower plasma K(+) concentration, suggesting significant differences in distal tubule adaptation to acute or chronic K(+) restriction. Twit Text FOAVip Mg(2+) restriction downregulates NCC through NEDD4-2 and prevents its activation by hypokalemia ????Am J Physiol Renal Physiol http://www.kidney.de/pget.php?&tw=1&pmid=31364380 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=31364380 #FOAvip English Wikipedia <ref>{{Cite pmid|31364380}}</ref> Mg(2+) restriction downregulates NCC through NEDD4-2 and prevents its activation by hypokalemia #MMPMID31364380 Ferdaus MZ; Mukherjee A; Nelson JW; Blatt PJ; Miller LN; Terker AS; Staub O; Lin DH; McCormick JA Am J Physiol Renal Physiol 2019[Oct]; 317 (4): F825-F838 PMID31364380show ga Hypomagnesemia is associated with reduced kidney function and life-threatening complications and sustains hypokalemia. The distal convoluted tubule (DCT) determines final urinary Mg(2+) excretion and, via activity of the Na(+)-Cl(-) cotransporter (NCC), also plays a key role in K(+) homeostasis by metering Na(+) delivery to distal segments. Little is known about the mechanisms by which plasma Mg(2+) concentration regulates NCC activity and how low-plasma Mg(2+) concentration and K(+) concentration interact to modulate NCC activity. To address this, we performed dietary manipulation studies in mice. Compared with normal diet, abundances of total NCC and phosphorylated NCC (pNCC) were lower after short-term (3 days) or long-term (14 days) dietary Mg(2+) restriction. Altered NCC activation is unlikely to play a role, since we also observed lower total NCC abundance in mice lacking the two NCC-activating kinases, STE20/SPS-1-related proline/alanine-rich kinase and oxidative stress response kinase-1, after Mg(2+) restriction. The E3 ubiquitin-protein ligase NEDD4-2 regulates NCC abundance during dietary NaCl loading or K(+) restriction. Mg(2+) restriction did not lower total NCC abundance in inducible nephron-specific neuronal precursor cell developmentally downregulated 4-2 (NEDD4-2) knockout mice. Total NCC and pNCC abundances were similar after short-term Mg(2+) or combined Mg(2+)-K(+) restriction but were dramatically lower compared with a low-K(+) diet. Therefore, sustained NCC downregulation may serve a mechanism that enhances distal Na(+) delivery during states of hypomagnesemia, maintaining hypokalemia. Similar results were obtained with long-term Mg(2+)-K(+) restriction, but, surprisingly, NCC was not activated after long-term K(+) restriction despite lower plasma K(+) concentration, suggesting significant differences in distal tubule adaptation to acute or chronic K(+) restriction. |Animals[MESH] |Diet[MESH] |Down-Regulation[MESH] |Hypokalemia/*metabolism[MESH] |Kidney Tubules, Distal/metabolism[MESH] |Magnesium Deficiency/genetics/*metabolism[MESH] |Magnesium/blood[MESH] |Mice[MESH] |Mice, Inbred C57BL[MESH] |Mice, Knockout[MESH] |Nedd4 Ubiquitin Protein Ligases/*biosynthesis/genetics[MESH] |Phosphorylation[MESH] |Potassium Deficiency/metabolism[MESH] |Potassium/blood[MESH]Mg(2+) restriction downregulates NCC through NEDD4-2 and prevents its (epmc).pdf DeepDyve Pubget Overpricing