Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Target Concepts:
Gene/Protein
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Query: UMLS:C0020500 (
hyperoxaluria
)
912
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hyperoxaluria
is a major risk factor for kidney stones and has no specific therapy, although
Oxalobacter formigenes
colonization is associated with reduced stone risk.
O. formigenes
interacts with colonic epithelium and induces colonic oxalate secretion, thereby reducing urinary oxalate excretion,
via
an unknown secretagogue. The difficulties in sustaining
O. formigenes
colonization underscore the need to identify the derived factors inducing colonic oxalate secretion. We therefore evaluated the effects of
O. formigenes
culture conditioned medium (CM) on apical
14
C-oxalate uptake by human intestinal Caco-2-BBE cells. Compared with control medium,
O. formigenes
CM significantly stimulated oxalate uptake (>2.4-fold), whereas CM from
Lactobacillus acidophilus
did not. Treating the
O. formigenes
CM with heat or
pepsin
completely abolished this bioactivity, and selective ultrafiltration of the CM revealed that the
O. formigenes
-derived factors have molecular masses of 10-30 kDa. Treatment with the protein kinase A inhibitor H89 or the anion exchange inhibitor 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid completely blocked the CM-induced oxalate transport. Knockdown of the oxalate transporter SLC26A6 also significantly restricted the induction of oxalate transport by CM. In a mouse model of primary hyperoxaluria type 1, rectal administration of
O. formigenes
CM significantly reduced (>32.5%) urinary oxalate excretion and stimulated (>42%) distal colonic oxalate secretion. We conclude that
O. formigenes
-derived bioactive factors stimulate oxalate transport in intestinal cells through mechanisms including PKA activation. The reduction in urinary oxalate excretion in hyperoxaluric mice treated with
O. formigenes
CM reflects the
in vivo
retention of biologic activity and the therapeutic potential of these factors.
...
PMID:
Oxalobacter formigenes-
Derived Bioactive Factors Stimulate Oxalate Transport by Intestinal Epithelial Cells. 2773 24
