Interaktion des hNaDC3 mit Fumarat und Fumaratderivaten

hNaDC3 and its interactions with fumararate and fumarate derivates

von Andrea Isabella Schmidt
Dissertation
Datum der mündl. Prüfung:2013-04-29
Erschienen:2013-04-22
Betreuer:Prof. Dr. Birgitta-Christina Burckhardt
Gutachter:PD Dr. Rotraut Mößner
Gutachter:Prof. Dr. Patricia Virsik-Köpp
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-3805

 

 

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Human NaDC3 is one of the five members of the “solute carrier 13 (SLC13)” gene family, all of them coding for electrogenic sodium-coupled transporters on plasma membranes. Transcripts of hNaDC3 have been detected in renal, hepatic, cerebral and placenta tissue. In a sodium-dependent symport it carries different dicarboxylates like succinate across the plasma membrane into the cytosol. Because of the increasing clinical relevance of fumarate and its derivates, we analysed the transport properties of hNaDC3 concerning these substrates, especially in comparison to succinate, a substrate of hNaDC3. First, we measured uptake of radiolabeled succinate in presence of sodium into hNaDC3- and vector-transfected HEK293 cells, adding fumarate, dimethylfumarate and diethylfumarate sequential to the extracellular solution. We only noticed inhibition of succinate uptake in presence of fumarate, showing affinity of hNaDC3 to fumarate, but not to diethylfumarate and dimethylfumarate. Second, we performed experiments using a two electrode voltage clamp device, measuring membrane currents in dependence of the substrates named above. Inward currents were could be identified under varied membrane potentials for the substrates succinate and fumarate. Again, there was no sign of transport activity noticeable for diethylfumarate and dimethylfumarate.
Keywords: hNaDC3, solute carrier, fumarate, diethylfumarate, dimethylfumarate
 
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