[Molecular physiological study of electrolyte transporters in renal tubular epithelial cells].
Patients with lifestyle-related diseases such as hypertension, diabetes, and hyperlipidemia are at high risk for the pathogenesis of a life-threatening atherosclerotic disease. The elucidation of the mechanism responsible for the pathogenesis can bring about the prevention and the cure of lifestyle-related diseases. We think that abnormal transport of electrolytes in renal tubule is involved in lifestyle-related diseases and renal failure. This review focuses on the regulatory mechanisms of Mg(2+) transport pathways in renal tubular cells. Mg(2+) filtrated by glomeruli is reabsorbed by transcellular and paracellular pathways in renal epithelial cells. Transient receptor potential melastatin 6 (TRPM6) channel is expressed in the apical membrane and involved in the reabsorption of Mg(2+). Cyclosporine A decreased TRPM6 expression and Mg(2+) influx, suggesting that the decrease in TRPM6 expression may cause hypomagnesemia. Claudin-16 is expressed in the tight junction (TJ) of the thick ascending limb of Henle and may be involved in the paracellular Mg(2+) transport. We found that the phosphorylation of claudin-16 is necessary for its localization on the TJ and claudin-16 is de-phosphorylated in Dahl salt-sensitive (DS) hypertensive rats. In epidemiologic studies, magnesium is the correlate of both systolic and diastolic blood pressure. Dysfunction of claudin-16 may be involved in the salt-sensitive hypertension. Dysfunction of Mg(2+) reabsorption in renal tubule may be involved in renal failure and lifestyle-related diseases.
Ikari
Akira
A
Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. ikari@u-shizuoka-ken.ac.jp
D000818:Animals; D057167:Claudins; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007684:Kidney Tubules / Q000378:metabolism*; D008019:Life Style; D008274:Magnesium / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D020303:Rats, Inbred Dahl; D051437:Renal Insufficiency / Q000209:etiology; D050053:TRPM Cation Channels / Q000502:physiology*
D057167:Claudins; D008565:Membrane Proteins; D050053:TRPM Cation Channels; C459082:TRPM6 protein, human; C502010:claudin 16; D008274:Magnesium