The Damage of Renal Brush Border Membrane in Fanconi's Syndrome Induced by 4-epi-Tetracycline

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The term "Fanconi's syndrome" describes a disturbance of proximal renal tubular function of multiple causation and comprising generalized hyperaminoaciduria, renal glucosuria, and hyperphosphaturia, as well as renal loss of potassium, bicarbonate and water, and other substances conserved by the proximal tubule. Ultrafiltered solutes as glucose, amino acids, phosphate and low molecular weight proteins are reabsorbed at proximal renal tubule through brush border membrane. It has been suggested that Fanconi's synd-rome is caused by the abnormality of transport carriers of renal brush border membrane. A reversible Fanconi's syndrome often occurs after ingestion of outdated tetracycline. This investigation aimed whether or not renal brush border membrane in Fanconi's syndrome induced by 4-epi-tetracycline (epi-TC) was damaged. Male albino rabbits, weighing about 2kg, received an intravenous injection of epi-TC (16mg/kg or 100mg/kg). One hour after the injection, renal brush border membrane was isolated by the continuous sucrose density gradient centrifugation method of Sacktor et al. The activities of γ-glutamyl transpeptidase (γ-GTP), alkaline phosphatase (AlP), trehalase and Na-K ATPase were measured. AlP of brush border membrane was investigated histochemically under electron microscope. SDS disc electrophoresis of brush border membrane proteins was performed. In control rabbits, the bulk of γ-GTP, AlP and trehalase activities immigrated to higher density fractions by the centrifugation than that of Na-K ATPase activity. On the other hand, in rabbits treated with 16mg/kg of epi-TC, the bulk of γ-GTP, AlP and trehalase activities was in lower density fractions than that of Na-K ATPase activity. In rabbits treated with 100mg/kg of epi-TC, the great bulk of γ-GTP, AlP and trehalase was in further lower density fractions. These data suggest that brush border membrane immigrated to low density fractions by the centrifugation in proportion to the dose of epi-TC. Electron micrographically, brush border membrane isolated from control rabbits was closed vesicle of membrane, whereas brush border membrane isolated from rabbits treated with 100mg/kg of epi-TC was open sheet of membrane. An electrophoretic pattern of brush border membrane proteins of rabbits treated with 100mg/kg of epi-TC differed from that of control rabbits. In experiment, the protein whose molecular weight was about 40,000 daltons was observed, not in control. We interpret these results as follows: One of proteins of brush border membrane was degradated by the injection of epi-TC and separated to subunits whose molecular weight was about 40,000 daltons. The degradation of this protein made brush border membrane fragile and the fragment of brush border membrane derived by the homogenizing operation became to the open sheet of membrane. The sedimentation constant would be decreased by this morphological changes of the fragment. Consequently, we detected the biochemical and morphological damages of renal brush border membrane in Fanconi's syndrome induced by epi-TC.
Japan Society of Clinical Chemistryの論文

The Damage of Renal Brush Border Membrane in Fanconi's Syndrome Induced by 4-epi-Tetracycline

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