Catalytic function of Drosophila melanogaster glutathione S‐transferase DmGSTS1‐1 (GST‐2) in conjugation of lipid peroxidation end products

Abstract

Drosophila melanogaster glutathione S‐transferase DmGSTS1‐1 (earlier designated as GST‐2) is related to sigma class GSTs and was previously described as an indirect flight muscle‐associated protein with no known catalytic properties. We now report that DmGSTS1‐1 isolated from Drosophila or expressed in Escherichia coli is essentially inactive toward the commonly used synthetic substrate 1‐chloro‐2,4‐dinitrobenzene (CDNB), but has relatively high glutathione‐conjugating activity for 4‐hydroxynonenal (4‐HNE), an electrophilic aldehyde derived from lipid peroxidation. 4‐HNE 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 P‐element insertions in the GstS1 gene have a reduced capacity for glutathione conjugation of 4‐HNE. In flies with both, one, or none of the GstS1 alleles disrupted by P‐element insertion, there is a linear correlation between DmGSTS1‐1 protein content and 4‐HNE‐conjugating activity. This correlation indicates that in adult Drosophila 70 ± 6% of the capacity to conjugate 4‐HNE is attributable to DmGSTS1‐1. The high abundance of DmGSTS1‐1 (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 S‐transferases (e.g. GSTA4‐4). The independent emergence of 4‐HNE‐conjugating activity in more than one branch of the glutathione S‐transferase superfamily suggests that 4‐HNE catabolism may be essential for aerobic life.

A novel Omega-class glutathione S-transferase gene in Apis cerana cerana: molecular characterisation of GSTO2 and its protective effects in oxidative stress

“…In addition, some Epsilon-class GSTs in mosquito have peroxidase activity and may be important in protection against oxidative stress (Lumjuan et al 2005;Ortelli et al 2003). The insect Sigma-class and Theta-class GSTs are implicated in the detoxification of lipid peroxidation products, suggesting a protective role against oxidative stress (Singh et al 2001;Yamamoto et al 2005). The Zeta-class GSTs may have common housekeeping functions in the tyrosine degradation pathway, including cellular defence against oxidative stress (Claudianos et al 2006).…”

Identification, genomic organization, and oxidative stress response of a sigma class glutathione S-transferase gene (AccGSTS1) in the honey bee, Apis cerana cerana

“…GSTs have also been found in large concentrations in other tissues. For example, DmGSTS1-1 was thought to be anchored to the flight muscle of D. melanogaster by the hydrophobic/acidic N-terminal extension and was demonstrated to be instrumental in protecting this highly aerobic tissue from by-products of oxidative stress (Singh et al 2001). Although this N-terminal extension on the sigma class GST also occurs in some other Muscamorphan insects, such as Musca domestica, Glossina morsitans, and Mayetola destructor, anchoring of this GST to the flight muscle is not universal.…”

“…They can catalyze the conjugation of the reduced glutathione (GSH) to electrophilic centers of a wide range of exogenous or endogenous toxic compounds, including cancer chemotherapeutic agents, chemical carcinogens, insecticides, herbicides, and oxidative stress products (Hayes et al 2005). Some members also manifest glutathione peroxidase activity and promote the metabolism of organic hydroperoxides generated in cells (Ayyadevara et al 2005;Burmeister et al 2008;Singh et al 2001;Tang and Tu 1994). As modulated expression levels of GST under oxidative stress are thought to represent Electronic supplementary material The online version of this article (doi:10.1007/s12192-012-0394-7) contains supplementary material, which is available to authorized users.…”

Expression profiles of seven glutathione S-transferase (GST) genes from Venerupis philippinarum exposed to heavy metals and benzo[a]pyrene

“…With regards to B[a]P exposure, the expression of VpGSTS1 showed a dramatic decrease, while VpGSTS2 and VpGSTS3 displayed notable increases with larger amplitude in VpGSTS2 (6.5 fold). It has been suggested that sigma class GSTs participate in cellular xenobiotic defenses and antioxidant systems in various organisms (Singh et al, 2001;Lee et al, 2008;Wan et al, 2008a;Nail and Choi, 2011;Won et al, 2011). For example, Tigriopus japonicus GST class sigma (GST-S) was observed to be more consistent than other types of GSTs both in concentration-and timedependent studies when exposed to hydrogen peroxide and heavy metals (Lee et al, 2008).…”