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Title: Dietary modulation of uptake transporters
Author: Naccarati, Chiara
ISNI:       0000 0004 5356 0650
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2014
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Transporters play a determinant role in creating and maintaining physiological balance within the cells. Though, not much information exists on the modulation of transporters, especially in terms of polyphenols and other dietary components. Initially, a comprehensive database was created, using the high-performance search engine Genevestigator. The database summarises the existing knowledge on selected transporters (OAT1, OAT3, OATP1A2, OATP1B1, OATP1B3, OATP4C1, MRP2, MRP3, BCRP, MCT1, MCT7 and SMCT1). The anatomical distribution of the latters was investigated in the human heart, kidney, liver and intestine. Transcriptional modulation was also assessed, in response to biological mediators, disease, chemicals and drugs. It was shown that while some transporters were modulated from a large number of conditions, others only responded to few. Interestingly, not many dietary compounds were tested, highlighting the limited knowledge existing in this area. Subsequently, expression of a transporter of interest, the organic anion transporter 3 (OAT3), was assessed in liver HepG2 cells. It was predicted, on the basis of the Ct value, that OAT3 was expressed in the cell line at low levels. Modulation of OAT3, in response to stressors (hydrogen peroxide, tert-butyl hydroperoxide and ethanol) at various concentrations and for different time lengths was assessed. It was shown that none of the stressors affected the transporter. In the same cell line, uptake of the metabolite kaempferol-3-O-glucuronide was assessed, to establish whether uptake occurred in a carrier-mediated manner or through passive diffusion mainly. Uptake resulted to be carrier-mediated, although the low Vmax of the transport, close to detection limit, did not make possible further studies to identify the transporter(s) involved in its uptake. Finally, intestine Caco-2 cells were used to assess modulation of the serotonin transporter from green tea and coffee. For the first time, it was reported that green tea and coffee acted as modulators of serotonin uptake. Whole extracts showed to act in a concentration-dependent way. Physiological concentrations of individual green tea components showed not to have a significant effect on the uptake, however significant effect was observed when using supplement concentrations (equivalent to 7 cups). Physiological concentrations of several coffee components showed to modulate serotonin uptake. Among them, ferulic acid and 5-feruloylquinic acid showed to act in a competitive manner.
Supervisor: Morgan, M. ; Bosch, C. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available