Untersuchung der Transportvorgänge des Prolyl-Hydroxylase-Hemmers ICA an den Transportern OAT1, OAT2, OAT3 und OAT4 von proximalen Nierentubuluszellen

Examination of transport processes of the prolyl hydroxylase inhibitor ICA on the transporters OAT1, OAT2, OAT3 and OAT4 of renal proximal tubule cells

by Kei Schulz
Doctoral thesis
Date of Examination:2017-12-05
Date of issue:2017-10-27
Advisor:Prof. Dr. Birgitta-Christina Burckhardt
Referee:Prof. Dr. Birgitta-Christina Burckhardt
Referee:Prof. Dr. Oliver Gross
Persistent Address: http://dx.doi.org/10.53846/goediss-6550

 

 

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Abstract

English

This thesis discusses the interactions between ICA and the organic anion transporters OAT1, OAT2, OAT3 and OAT4. ICA is a substance which can inhibit the prolyl hydroxylase domain. This leads to an upregulation of hypoxia inducible factor (HIF). Artificial upregulation of HIF has got the opportunity to protect the organism from hypoxia related diseases and effects. Renal ischemia plays an important part in the pathogenesis of acute and chronic kidney failure. To measure the impact of ICA on the different organic anion transporters uptake experiments with these transporters stably transfected in human embryonic kidney 293 cells and its reference substrates were carried out. The first question was whether there is any interaction or inhibition of the organic anion transporters. To quantify the inhibition the half maximal inhibitory concentration was measured for each OAT. In the last step it was examined whether ICA is transported by the organic anion transporters. The results show that OAT1, OAT3 and OAT4 are inhibited by ICA whereas OAT2 only marginally interacts with ICA. Furthermore, ICA is transported by OAT3 and OAT4. In conclusion the results of this thesis strengthen the hypothesis that ICA can be transported by the organic anion transporters into the proximal tubule cells to upregulate HIF and prevent hypoxia induced kidney failure.
Keywords: organic anion transporter; OAT; PHD inhibitor; ICA; hypoxia; HEK293
 
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