| Autor: |
Frey, I.M., Rubio-Aliaga, I., Siewert, A., Sailer, D., Drobyshev, A., Beckers, J., Hrabě de Angelis, M., Aubert, J., Bar Hen, A., Fiehn, O., Eichinger, H.M., Daniel, H. |
| Jazyk: |
němčina |
| Rok vydání: |
2007 |
| Předmět: |
|
| Zdroj: |
Physiol. Genomics 28, 301-310 (2007) |
| Popis: |
PEPT2 is an integral membrane protein in the apical membrane of renal epithelial cells that operates as a rheogenic transporter for di- and tripeptides and structurally related drugs. Its prime role is thought to be the reabsorption of filtered di- and tripeptides contributing to amino acid homeostasis. To elucidate the role of PEPT2 in renal amino acid metabolism we submitted kidney tissues of wild-type and a Pept2–/– mouse line to a comprehensive transcriptome, proteome and metabolome profiling and analyzed urinary amino acids and dipeptides. cDNA microarray analysis identified 147 differentially expressed transcripts in transporter-deficient animals, and proteome analysis by 2D-PAGE and MALDI-TOF-MS identified 37 differentially expressed proteins. Metabolite profiling by GC-MS revealed predominantly altered concentrations of amino acids and derivatives. Urinary excretion of amino acids demonstrated increased glycine and cysteine/cystine concentrations and dipeptides in urine were assessed by amino acid analysis of urine samples before and after in vitro dipeptidase digestion. Dipeptides constituted a noticeable fraction of urinary amino acids in Pept2–/– animals, only, and dipeptide-bound glycine and cystine were selectively increased in Pept2–/– urine samples. These findings were confirmed by a drastically increased excretion of cysteinyl-glycine (cys-gly). Urinary loss of cys-gly together with lower concentrations of cysteine, glycine, and oxoproline in kidney tissue and altered expression of mRNA and proteins involved in glutathione (GSH) metabolism suggests that PEPT2 is predominantly a system for reabsorption of cys-gly originating from GSH break-down, thus contributing to resynthesis of GSH. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
