Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary hyperoxaluria type 1 is a severe kidney stone disease caused by abnormalities of the peroxisomal alanine-glyoxylate aminotransferase (AGT). The most frequent mutation G170R results in aberrant mitochondrial localization of the active enzyme. To evaluate the population of peroxisome-localized AGT, we developed a quantitative Glow-AGT assay based on the self-assembly split-GFP approach and used it to identify drugs that can correct mislocalization of the mutant protein. In line with previous reports, the Glow-AGT assay showed that mitochondrial transport inhibitors DECA and monensin increased peroxisomal localization of the mutant. Here, we demonstrate that prolonged treatment with the translation elongation inhibitor emetine, a medicinal alkaloid used in treatment of amoebiasis, corrected G170R-AGT mislocalization. Furthermore, emetine reduced the augmented oxalate level in culture media of patient-derived hepatocytes bearing the G170R mutation. A distinct translation inhibitor GC7 had a similar effect on the mutant Glow-AGT relocalization indicating that mild translation inhibition is a promising therapeutic approach for primary hyperoxaluria type 1 caused by AGT misfolding/mistargeting.
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PMID:Translation inhibition corrects aberrant localization of mutant alanine-glyoxylate aminotransferase: possible therapeutic approach for hyperoxaluria. 2977 53