Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes.
o-Quinones are physiological oxidation products of catecholamines that contribute to redox cycling, toxicity and apoptosis, i.e. the neurodegenerative processes underlying Parkinson's disease and schizophrenia. The present study shows that the cyclized o-quinones aminochrome, dopachrome, adrenochrome and noradrenochrome, derived from dopamine, dopa, adrenaline and noradrenaline respectively, are efficiently conjugated with glutathione in the presence of human glutathione transferase (GST) M2-2. The oxidation product of adrenaline, adrenochrome, is less active as a substrate for GST M2-2, and more efficiently conjugated by GST M1-1. Evidence for expression of GST M2-2 in substantia nigra of human brain was obtained by identification of the corresponding PCR product in a cDNA library. Glutathione conjugation of these quinones is a detoxication reaction that prevents redox cycling, thus indicating that GSTs have a cytoprotective role involving elimination of reactive chemical species originating from the oxidative metabolism of catecholamines. In particular, GST M2-2 has the capacity to provide protection relevant to the prevention of neurodegenerative diseases.
Baez
S
S
Unit of Biochemical Toxicology, Department of Biochemistry, Stockholm University, Wallenberg Laboratory, S-106 91 Stockholm.
Segura-Aguilar
J
J
Widersten
M
M
Johansson
A S
AS
Mannervik
B
B
D000323:Adrenochrome / Q000378:metabolism; D000975:Antioxidants; D002395:Catecholamines / Q000378:metabolism*; D003001:Cloning, Molecular; D017931:DNA Primers; D004926:Escherichia coli; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D045563:Indolequinones; D007211:Indoles / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D009410:Nerve Degeneration; D011809:Quinones / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity
D000975:Antioxidants; D002395:Catecholamines; D017931:DNA Primers; D045563:Indolequinones; D007211:Indoles; D007527:Isoenzymes; D011809:Quinones; D011994:Recombinant Proteins; C001123:dopachrome; C088462:noradrenochrome; D000323:Adrenochrome; D005982:Glutathione Transferase