The effect of oxidants, electrophiles, and NO donors in rat or human erythrocytes was analyzed to investigate the influence of protein sulfhydryl groups on the metabolism of these thiol reactants. Oxidant-evoked alterations in thiolic homeostasis were significantly different in the two models; large amounts of glutathione protein mixed disulfides were produced in rat but not in human erythrocytes by treatment with hydroperoxides or diamide. The disappearance of all forms of glutathione (reduced, disulfide, protein mixed disulfide) was induced by menadione only in human erythrocytes. The treatment of rat red blood cells with electrophiles produced glutathione S-conjugates to a much lower extent than in human red blood cells; GSH was only minimally depleted in rat red blood cells. The NO donor S-nitrosocysteine induced a rapid transnitrosation reaction with hemoglobin in rat erythrocytes producing high levels of S-nitrosohemoglobin; this reaction in human red blood cells was negligible. All drugs were cleared more rapidly in rat than in human erythrocytes. Unlike human Hb, rat hemoglobin contains three families of protein SH groups; one of these located at position β125 is directly implicated in the metabolism of thiol reactants. This is thought to influence significantly the biochemical, pharmacological, and toxicological effects of some drugs.

Rossi, R., Milzani, A., DALLE DONNE, I., Giannerini, F., Giustarini, D., Lusini, L., et al. (2001). Different metabolizing ability of thiol reactants in human and rat blood: biochemical and pharmacological implications. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 276(10), 7004-7010 [10.1074/jbc.M005156200].

Different metabolizing ability of thiol reactants in human and rat blood: biochemical and pharmacological implications.

ROSSI, RANIERI;GIUSTARINI D;CHERUBINI DI SIMPLICIO, PAOLO
2001

Abstract

The effect of oxidants, electrophiles, and NO donors in rat or human erythrocytes was analyzed to investigate the influence of protein sulfhydryl groups on the metabolism of these thiol reactants. Oxidant-evoked alterations in thiolic homeostasis were significantly different in the two models; large amounts of glutathione protein mixed disulfides were produced in rat but not in human erythrocytes by treatment with hydroperoxides or diamide. The disappearance of all forms of glutathione (reduced, disulfide, protein mixed disulfide) was induced by menadione only in human erythrocytes. The treatment of rat red blood cells with electrophiles produced glutathione S-conjugates to a much lower extent than in human red blood cells; GSH was only minimally depleted in rat red blood cells. The NO donor S-nitrosocysteine induced a rapid transnitrosation reaction with hemoglobin in rat erythrocytes producing high levels of S-nitrosohemoglobin; this reaction in human red blood cells was negligible. All drugs were cleared more rapidly in rat than in human erythrocytes. Unlike human Hb, rat hemoglobin contains three families of protein SH groups; one of these located at position β125 is directly implicated in the metabolism of thiol reactants. This is thought to influence significantly the biochemical, pharmacological, and toxicological effects of some drugs.
Rossi, R., Milzani, A., DALLE DONNE, I., Giannerini, F., Giustarini, D., Lusini, L., et al. (2001). Different metabolizing ability of thiol reactants in human and rat blood: biochemical and pharmacological implications. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 276(10), 7004-7010 [10.1074/jbc.M005156200].
File in questo prodotto:
File Dimensione Formato  
2001 Rossi JBC.pdf

accesso aperto

Tipologia: PDF editoriale
Licenza: PUBBLICO - Pubblico con Copyright
Dimensione 257.99 kB
Formato Adobe PDF
257.99 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/435847