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Ponte Academic Journal
Jan 2015, Volume 71, Issue 1

Water Channel Proteins (Aquaporins): From their Discovery in 1985 in Cluj-Napoca, Romania (By the use of a Doping Nmr Method and Specific Labeling) to the use of their Inhibitors as Magic Bullets

Author(s): BENGA G

J. Ponte - Jan 2015 - Volume 71 - Issue 1



Abstract:
Water channels or water channel proteins (WCPs) are transmembrane proteins that have a specific three-dimensional structure with a pore that can be permeated by water molecules. The first WCP was discovered in the human red blood cell membrane in Cluj-Napoca, Romania, in 1985 by Bengas group. We have measured the water permeability of human red blood cells (RBCs) by a doping NMR method. We showed for the first time by NMR that the parameters characterizing diffusional water permeability are the same in RBCs and resealed ghosts and reported the largest series of determinations of water diffusional permeability of RBCs available in literature. The first water channel protein (WCP), later called aquaporin 1 (AQP1) was discovered in the RBC membrane by my group in 1985 in Cluj-Napoca, Romania, reported in publications in 1986 (Benga et al., Biochemistry, 25, 1535-1538, 1986; Benga et al., Eur. J. Cell Biol., 41, 252-262, 1986) and reviewed in the following years. This discovery was achieved by specific labelling of the RBC membranes with the known water transport inhibitor 203Hg - p-chloromercuribenzenesulfonate (PCMBS). In parallel, the water permeability was measured by the doping NMR technique and the inhibition induced by PCMBS was calculated. The priority of Benga in the discovery of the first WCP was acknowledged by many outstanding scientists. We also have a world priority in the discovery of the implications of water channel proteins in epilepsy (Benga and Morariu, Nature, 265, 636-638, 1977) and Duchenne muscular dystrophy (Serbu et al., Muscle & Nerve, 9, 243-247, 1986). These findings were interpreted as an expression of generalized membrane defects affecting water permeability in epilepsy and Duchenne muscular dystrophy. In recent years this idea was confirmed. Since the discovery of WCPs tremendous progress in understanding their role in physiology and pathology. Based on these advances it became clear that inhbitors of AQPs can be used as magic bullets in a variety of diseases, including cancer. The doping NMR method should be used to compare the effects of inhibitors of WCPs as magic bullets. Examples of this approach will be given.
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