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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Anti-Bacterial Agents, Carrier Proteins, Endocytosis, Endosomes, Gentamicins, In Vitro Techniques, Kidney Cortex, Kidney Medulla, Lysosomes, Male, Microvilli, RNA, Messenger, Rats, Rats, Sprague-Dawley, Sodium-Phosphate Cotransporter Proteins, Sodium-Phosphate Cotransporter Proteins, Type II, Symporters.
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Does gentamicin cause endocytosis of Na/Pi cotransporter protein ( NaPi-2 )? Context: Renal toxicity is a major side-effect of aminoglycoside antibiotics and is characterized by an early impairment in proximal tubular function. In a previous study, we have shown that gentamicin administration to the rat causes an early impairment in sodium gradient-dependent phosphate (Na/Pi) cotransport activity. The purpose of our current study was to determine the molecular mechanisms of the impairment in Na/Pi cotransport activity, specifically the role of the proximal tubular type II Na/Pi cotransporter. Rats were treated for one, two, and three days with two daily injections of 30 mg/kg body weight gentamicin or the vehicle. Gentamicin caused a progressive decrease in superficial cortical apical brush-border membrane (SC-BBM) Na/Pi cotransporter activity (856 +/- 93 in control vs. 545 +/- 87 pmol/mg BBM protein in 3-day gentamicin, P < 0.01). Western blot analysis showed a parallel and progressive decrease in SC-BBM Na/Pi cotransporter protein abundance, a 50% decrease after one day of treatment, a 63% decrease after two days of treatment, and an 83% decrease after three days treatment with gentamicin. In contrast, gentamicin treatment had no effect on Na/Pi cotransport activity or Na/Pi cotransporter protein abundance in BBM isolated from the juxtamedullary cortex (JMC-BBM). Immunofluorescence microscopy showed a major decrease in the expression of Na/Pi cotransporter protein in the apical membrane of the proximal convoluted tubule, with progressive intracellular accumulation of Na/Pi protein. Colocalization studies showed that in gentamicin-treated rats, Na/Pi protein was colocalized in the early endosomes and especially in the lysosomes. Northern blot analysis of cortical RNA interestingly showed no reduction in Na/Pi cotransporter mRNA abundance even after three days of gentamicin treatment.
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We conclude that gentamicin inhibits Na/Pi cotransport activity by causing a decrease in the expression of the type II Na/Pi cotransport protein at the level of the proximal tubular apical BBM and that inhibition of Na/Pi cotransport activity is most likely mediated by post-transcriptional mechanisms. Final Decision: yes