Abstract
Glutathione transferases (GSTs) are enzymes devoted to the protection of cells against many different toxins. In erythrocytes, the isoenzyme (e-GST) mainly present is GSTP1-1, which is overexpressed in humans in case of increased blood toxicity, as it occurs in nephrophatic patients or in healthy subjects living in polluted areas. The present study explores the possibility that e-GST may be used as an innovative and highly sensitive biomarker of blood toxicity also for other mammals. All distinct e-GSTs from humans, Bos taurus (cow), Sus scrofa (pig), Capra hircus (goat), Equus caballus (horse), Equus asinus (donkey) and Ovis aries (sheep), show very similar amino acid sequences, identical kinetics and stability properties. Reference values for e-GST in all these mammals reared in controlled farms span from 3.5±0.2 U/gHb in the pig to 17.0±0.9 U/gHb in goat; such activity levels can easily be determined with high precision using only a few microliters of whole blood and a simple spectrophotometric assay. Possibly disturbing factors have been examined to avoid artifact determinations. This study provides the basis for future screening studies to verify if animals have been exposed to toxicologic insults. Preliminary data on cows reared in polluted areas show increased expression of e-GST, which parallels the results found for humans.
Highlights
Glutathione transferases (GSTs) are a superfamily of detoxifying enzymes devoted to inactivate a large variety of different toxic compounds.[1,2] They catalyze the conjugation of glutathione to many organic compounds, so that it can be more eliminated from the organism.[1,2] they can act like ligandins sequestering toxic molecules including iron nitric oxide complexes.[3]
It has been observed that the human erythrocyte GSTP1-1 (e-glutathione transferase (GST)) is overexpressed in the case of increased blood toxicity as it occurs in healthy subjects living in polluted areas and in nephrologic patients under conservative or dialytic therapies.[5,6,7,8]
Of interest is the strict conservation of the four cysteines (Cys[14], Cys[47], Cys[101] and Cys169) that confer peculiar redox sensitivity to this enzyme. Both in human and horse e-GSTs, many oxidizing chemicals may induce the formation of an intra-chain disulfide involving the two highly reactive cysteines, that is, Cys[47] and Cys101.9,10 These oxidized forms are completely inactive, but they can be reactivated under reducing treatment with DTT at alkaline pH values
Summary
Glutathione transferases (GSTs) are a superfamily of detoxifying enzymes devoted to inactivate a large variety of different toxic compounds.[1,2] They catalyze the conjugation of glutathione to many organic compounds, so that it can be more eliminated from the organism.[1,2] they can act like ligandins sequestering toxic molecules including iron nitric oxide complexes.[3]. The dimeric cytosolic GSTs are abundantly expressed in many tissues and grouped into seven distinct isoenzyme classes termed alpha, pi, mu, omega, sigma, theta and zeta.[1,2] The only GST belonging to the pi class is GSTP1-1, an interesting enzyme that is mainly present in erythrocytes, brain, lung and skin This isoenzyme is involved in the modulation of the apoptotic cascade through its interaction with cJNK.[4] Recently, it has been observed that the human erythrocyte GSTP1-1 (e-GST) is overexpressed in the case of increased blood toxicity as it occurs in healthy subjects living in polluted areas and in nephrologic patients under conservative or dialytic therapies.[5,6,7,8] Interestingly, the expression of this enzyme does not fulfill an instantaneous snapshot of the blood toxicity, but an average value over a time span of about 2/3 months (corresponding to the mean life of the erythrocyte) as it is exclusively expressed during erythropoiesis.[5]. The presence of interfering factors like the occurrence of the inactive oxidized form of e-GST9 has been examined
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