Aryl hydrocarbon receptor (AhR) and its endogenous agonist-indoxyl sulfate in chronic kidney disease.

T Kamiński, M Michałowska… - Postepy Higieny i …, 2017 - europepmc.org
T Kamiński, M Michałowska, D Pawlak
Postepy Higieny i Medycyny Doswiadczalnej (Online), 2017europepmc.org
The indoxyl sulfate (IS, indoxyl sulphate) is the end product of dietary tryptophan
degradation by indole pathway and significantly higher serum and tissue concentrations of
this compound is observed in patients with impaired renal function. Despite the high albumin
binding affinity, the remaining free fraction of IS has a number of biological effects related to
the generation of oxidative stress andactivation of signaling pathways related to NF-кB, p53
protein, STAT3, TGF-β and Smad2/3. IS induces the inflammatory process, exerts …
The indoxyl sulfate (IS, indoxyl sulphate) is the end product of dietary tryptophan degradation by indole pathway and significantly higher serum and tissue concentrations of this compound is observed in patients with impaired renal function. Despite the high albumin binding affinity, the remaining free fraction of IS has a number of biological effects related to the generation of oxidative stress andactivation of signaling pathways related to NF-кB, p53 protein, STAT3, TGF-β and Smad2/3. IS induces the inflammatory process, exerts nephrotoxic activity and is also a factor impairing the cardiovascular system. Its high concentrations are associated with the occurrence of cardiovascular incidents, whose frequency is significantly higher in patients with chronic kidney disease. Evaluation of the mechanisms that underlie the high reactivity of indoxyl sulfate and its biological effects showed that this compound is an agonist of the aryl hydrocarbon receptor (AhR). This receptor plays an important role in maintaining homeostasis Moreover, AhR exerts high transcriptional activity, so ligands of obciążethis receptor may exert different biological effects. The following paper describes the role of indoxyl sulfate as AhR ligand in the context of the excessive accumulation, which appears as one of the symptoms associated with chronic kidney disease.
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