A 1 H spin echo and 51 V NMR study of the interaction of vanadate with intact erythrocytes

Garner, M., Reglinski, J., Smith, W. E., McMurray, J. , Abdullah, I. and Wilson, R. (1997) A 1 H spin echo and 51 V NMR study of the interaction of vanadate with intact erythrocytes. Journal of Biological Inorganic Chemistry, 2(2), pp. 235-241. (doi:10.1007/s007750050129)

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Abstract

The action of vanadate on intact human erythrocytes was studied by 1H spin echo and 51V NMR spectroscopy as a model for the behaviour of vanadium(V) complexes in experimental diabetes. Vanadate is reduced by the intact erythrocyte at the expense of intracellular glutathione which rapidly depletes from the intracellular volume. Using the blocking agent 4,4′-diisothio-cyanatostilbene-2,2′-disulfonic acid (DIDS), which specifically blocks the anion transporter, vanadate reduction could be inhibited and glutathione depletion arrested. Thus, for the reaction with the intact cell to occur, vanadium(V) must cross the cell wall, possibly via the anion transporter. Nitrofurantoin was used to inhibit glutathione reductase in the erythrocyte suspensions. Under these conditions, treatment of the cells with vanadate induced glutathione oxidation prior to depletion. A study of the reaction of vanadate with haemolysate indicates that, without the influence of the membrane, rapid oxidation of glutathione to glutathione disulfide by the vanadyl cation occurs with no glutathione depletion, and that under these conditions vanadate reduction is incomplete. This study generates a model for the behaviour of vanadium complexes in vivo, providing a basis for the rational design and synthesis of new vanadium-based agents as insulin mimics. In essence, vanadium is transported across the membrane as vanadate(V), is reduced in situ by glutathione, and becomes complexed to a wide range of intracellular binding sites. Exchange reactions between glutathione and sulfhydryl groups present on haemoglobin and membrane lead to the depletion of glutathione from the cytosol.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McMurray, Professor John
Authors: Garner, M., Reglinski, J., Smith, W. E., McMurray, J., Abdullah, I., and Wilson, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Biological Inorganic Chemistry
Publisher:Springer
ISSN:0949-8257
ISSN (Online):1432-1327

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