Primary hyperoxalurias (PHs) are rare inborn errors of glyoxylate metabolism
characterized by excessive synthesis and excretion of the metabolic end-product oxalate
and the progressive accumulation of insoluble calcium oxalate in the kidney and urinary
tract. About one third of the cases of Primary hyperoxaluria type 1 (PH1) is due to a unique
protein trafficking defect in which AGT is mistargeted from peroxisomes to mitochondria,
where it is metabolically useless. Pharmacological chaperones have been shown to correct
protein misfolding in several genetic diseases.
We aimed to test the effect of B6-vitamers (PM, PL, PN) on AGT mitochondrial
mistargeting in primary culture of hepatocytes from AGT*LRM mice, which express the
mutant mistargeting AGT protein (with mutation G170R in the minor haplotype of human
AGT). Using image analysis tools and statistics coefficient to quantify the degree of “AGT
mistargeting”.
