Work

Is the glutathione conjugate of trans-4-hydroxy-2-nonenal transported by the multispecific organic anion transporting-ATPase of human erythrocytes?

Year: 1998

Type: article

Abstract: Trans-4-hydroxy-2-nonenal (4-HNE), a cytotoxic end product of lipid peroxidation, is present in normal human blood plasma at concentrations of 0.1-1.0 microM. It can be, however, further metabolized within a cell, and one of the main products is 4-HNE glutathione conjugate (HNE-SG). In human erythrocyte membrane the system for active extrusion of glutathione (GSH) conjugates of various endo- and xenobiotics has been described; it exhibits either a low (Km at submillimolar concentration range) or a high (Km at low micromolar range) affinity for the transported substrates, such as for example S-(2,4-dinitrophenyl)glutathione (Dnp-SG). In the present study it has been shown that the high affinity transport system for Dnp-SG is competitively inhibited by HNE-SG with Ki of 0.2 microM, while 4-HNE inhibits non-competitively the activity of the transport system for Dnp-SG with Ki of 220microM. These observations point to the possibility that HNE-SG shares the same transport system with GSH conjugates of other endo- and xenobiotics in erythrocytes. This may be of importance for overall detoxification of the organism under oxidative stress.

Source: Acta Biochimica Polonica

DOI: 10.18388/abp.1998_4318

Authors: A Dygas, P Makowski, S Pikuła

Institution: Instytut Biologii Doświadczalnej im. Marcelego Nenckiego

Language: English

Topic: Drug Transport and Resistance Mechanisms

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $1,750