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Catalytic function of Drosophila melanogaster glutathione Sâtransferase DmGSTS1â1 (GSTâ2) in conjugation of lipid peroxidation end products
- Singh, Sharda P., Coronella, Julia A., BeneÅ¡, Helen, Cochrane, Bruce J., Zimniak, Piotr
- European journal of biochemistry 2001 v.268 no.10 pp. 2912-2923
- Drosophila melanogaster, Escherichia coli, adults, alleles, cytotoxicity, etiology, flight, flight muscles, glutathione, glutathione transferase, imagos, insects, lipid peroxidation, mammals, metabolism, oxidation, oxidative stress, protective effect, protein content, tissues
- Drosophila melanogaster glutathione Sâtransferase DmGSTS1â1 (earlier designated as GSTâ2) is related to sigma class GSTs and was previously described as an indirect flight muscleâassociated protein with no known catalytic properties. We now report that DmGSTS1â1 isolated from Drosophila or expressed in Escherichia coli is essentially inactive toward the commonly used synthetic substrate 1âchloroâ2,4âdinitrobenzene (CDNB), but has relatively high glutathioneâconjugating activity for 4âhydroxynonenal (4âHNE), an electrophilic aldehyde derived from lipid peroxidation. 4âHNE is thought to have signaling functions and, at higher concentrations, has been shown to be cytotoxic and involved in the etiology of various degenerative diseases. Drosophila strains carrying Pâelement insertions in the GstS1 gene have a reduced capacity for glutathione conjugation of 4âHNE. In flies with both, one, or none of the GstS1 alleles disrupted by Pâelement insertion, there is a linear correlation between DmGSTS1â1 protein content and 4âHNEâconjugating activity. This correlation indicates that in adult Drosophila 70âÂ±â6% of the capacity to conjugate 4âHNE is attributable to DmGSTS1â1. The high abundance of DmGSTS1â1 (approximately 2% of the soluble protein in adult flies) and its previously reported localization in tissues that are either highly aerobic (indirect flight muscle) or especially sensitive to oxidative damage (neuronal tissue) suggest that the enzyme may have a protective role against deleterious effects of oxidative stress. Such function in insects would be analogous to that carried out in mammals by specialized alpha class glutathione Sâtransferases (e.g. GSTA4â4). The independent emergence of 4âHNEâconjugating activity in more than one branch of the glutathione Sâtransferase superfamily suggests that 4âHNE catabolism may be essential for aerobic life.