Proteoliposomes as Tool for Assaying Membrane Transporter Functions and Interactions with Xenobiotics

Pharmaceutics

Mariafrancesca Scalise¹  Lorena Pochini¹  Nicola Giangregorio²  Annamaria Tonazzi² 

[1] Laboratory of Biochemistry and Molecular Biotechnology, Department BEST (Biology, Ecology and Earth Sciences), University of Calabria, Via P. Bucci 4c, Arcavacata di Rende 87036, Italy; E-Mails:;CNR Institute of Biomembranes and Bioenergetics, via Amendola 165/A, Bari 70126, Italy; E-Mails:

关键词: proteoliposomes;    transport;    drugs;    xenobiotics;    reconstitution;    drug discovery;   

DOI  :  10.3390/pharmaceutics5030472

来源: mdpi

【 摘 要 】

Proteoliposomes represent a suitable and up to date tool for studying membrane transporters which physiologically mediate absorption, excretion, trafficking and reabsorption of nutrients and metabolites. Using recently developed reconstitution strategies, transporters can be inserted in artificial bilayers with the same orientation as in the cell membranes and in the absence of other interfering molecular systems. These methodologies are very suitable for studying kinetic parameters and molecular mechanisms. After the first applications on mitochondrial transporters, in the last decade, proteoliposomes obtained with optimized methodologies have been used for studying plasma membrane transporters and defining their functional and kinetic properties and structure/function relationships. A lot of information has been obtained which has clarified and completed the knowledge on several transporters among which the OCTN sub-family members, transporters for neutral amino acid, B0AT1 and ASCT2, and others. Transporters can mediate absorption of substrate-like derivatives or drugs, improving their bioavailability or can interact with these compounds or other xenobiotics, leading to side/toxic effects. Therefore, proteoliposomes have recently been used for studying the interaction of some plasma membrane and mitochondrial transporters with toxic compounds, such as mercurials, H₂O₂ and some drugs. Several mechanisms have been defined and in some cases the amino acid residues responsible for the interaction have been identified. The data obtained indicate proteoliposomes as a novel and potentially important tool in drug discovery.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.