Dietary salt intake activates MAP kinases in the rat kidney.
This study explored the hypothesis that dietary salt promoted changes in renal expression of TGF-beta1 and NOS3 by modulating the mitogen-activated protein kinase (MAPK) pathways. Sprague-Dawley rats were maintained for four days on formulated diets that contained 0.3, 1.0, 3.0, or 8.0% NaCl. An increase in salt intake to greater than or equal to 3.0% NaCl increased kinase activities of p38 MAPK and p42/44 MAPK, but not p46/54 JNK/SAPK, in the cortex and outer and inner medulla. Associated with this increased activity was a relative increase in the phosphorylated forms of the transcription factors ATF-2 and Elk-1. Compared with rats on 0.3% NaCl diet, glomerular preparations from rats on 8.0% NaCl diet contained more NOS3 and produced greater amounts of total and active TGF-beta1 and NOx. PD-098059, a MEK1 inhibitor, and SB-203580, an inhibitor of p38 MAPKalpha-gamma, diminished NOS3 expression and production of TGF-beta1 and NOx. TEA, administered intravenously 5 min before harvesting kidneys of rats on the 8.0% NaCl diet, decreased activities of both p38 MAPK and p42/44 MAPK, compared with vehicle-treated animals. Thus, an increase in dietary salt activated through a TEA-sensitive pathway the p38 MAPK and p42/44 MAPK signaling cascades, which promoted the increase in glomerular TGF-beta1 and NOS3 expression.
Nephrology Research and Training Center, University of Alabama at Birmingham, Alabama 35294-0007, USA.
Wei-Zhong
WZ
Ying
Paul W
PW
Sanders
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D019789:Tetraethylammonium / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D017673:Sodium Chloride, Dietary; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019789:Tetraethylammonium; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one