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Localization of members of the MCT monocarboxylate transporter family Slc16 in the kidney and regulation during metabolic acidosis

The monocarboxylate transporter family (MCT) comprises 14 members with distinct transport properties and tissue distribution. The kidney expresses several members of the MCT family, but only little is known about their exact distribution and function. Here we investigated selected members of the MCT family in mouse kidney. MCT1, MCT2, MCT7 and MCT8 localized to basolateral membranes of the epithelial cells lining the nephron. MCT1 and MCT8 were detected in proximal tubule cells whereas MCT7 and MCT2 were located in the thick ascending limb. MCT7 was also found in the distal tubule. CD147, a β-subunit of MCT1 and MCT4, showed partially overlapping expression with MCT1 and MCT2. However, CD147 was also found in intercalated cells. We also detected SMCT1 and SMCT2, two Na+-dependent monocarboxylate cotransporters, on the luminal membrane of type A intercalated cells. Transcriptome analysis of mouse kidney during acid-loading had found alterations in the mRNA abundance of several Slc16 transporters. Thus, mice were given an acid-load for 2 and 7 days. Acidotic animals showed a marked but transient increase in urinary lactate excretion. During acidosis, a down-regulation of MCT1, MCT8, and SMCT2 was observed at mRNA level, whereas MCT7 and SMCT1 showed increased mRNA abundance. Only MCT2 and MCT7 showed lower protein abundance whereas all other transporters remained unchanged. In summary, we describe for the first time the localization of various MCT transporters in mammalian kidney and demonstrate that metabolic acidosis induces a transient increase in urinary lactate excretion paralleled by lower MCT2 and MCT7 protein expression.

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ABSTRACT The monocarboxylate transporter family (MCT) comprises 14 members with distinct transport properties and tissue distribution. The kidney expresses several members of the MCT family, but only little is known about their exact distribution and function. Here we investigated selected members of the MCT family in mouse kidney. MCT1, MCT2, MCT7 and MCT8 localized to basolateral membranes of the epithelial cells lining the nephron. MCT1 and MCT8 were detected in proximal tubule cells whereas MCT7 and MCT2 were located in the thick ascending limb. MCT7 was also found in the distal tubule. CD147, a β-subunit of MCT1 and MCT4, showed partially overlapping expression with MCT1 and MCT2. However, CD147 was also found in intercalated cells. We also detected SMCT1 and SMCT2, two Na+-dependent monocarboxylate cotransporters, on the luminal membrane of type A intercalated cells. Transcriptome analysis of mouse kidney during acid-loading had found alterations in the mRNA abundance of several Slc16 transporters. Thus, mice were given an acid-load for 2 and 7 days. Acidotic animals showed a marked but transient increase in urinary lactate excretion. During acidosis, a down- regulation of MCT1, MCT8, and SMCT2 was observed at mRNA level, whereas MCT7 and SMCT1 showed increased mRNA abundance. Only MCT2 and MCT7 showed lower protein abundance whereas all other transporters remained unchanged. In summary, we describe for the first time the localization of various MCT transporters in mammalian kidney and demonstrate that metabolic acidosis induces a transient increase in urinary lactate excretion paralleled by lower MCT2 and MCT7 protein expression. 1

Tesi di Dottorato

Dipartimento: Nefrologia

Autore: Angelica Perna Contatta »

Composta da 75 pagine.

 

Questa tesi ha raggiunto 179 click dal 15/04/2010.

Disponibile in PDF, la consultazione è esclusivamente in formato digitale.