Activation versus inhibition of microsomal glutathione S-transferase activity by acrolein. Dependence on the concentration and time of acrolein exposure. (25th September 2017)

• Record Type: Journal Article
• Authors: Sthijns, Mireille M.J.P.E.; den Hartog, Gertjan J.M.; Scasso, Caterina; Haenen, Jan P.; Bast, Aalt; Haenen, Guido R.M.M.
• Is Part Of: Chemico-biological interactions. Volume 275(2017)
• Page Start: 116
• Page End: 120
• Publication Date: 2017-09-25
• Subjects: Acrolein -- Adaptation -- Glutathione -- Microsomal GSH S-transferase; CDNB 1-chloro-2, 4-dinitrobenzene -- FDNB 1-Fluoro-2, 4-dinitrobenzene -- GSH Glutathione -- HPLC High Performance Liquid Chromatography -- MAPEG membrane-associated proteins in eicosanoid and glutathione metabolism -- MGST Microsomal Glutathione Transferase -- NEM N-ethylmaleimide -- PGO phenylglyoxal; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2017.08.001
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: The toxicity of acrolein, an α, β-unsaturated aldehyde, is due to its soft electrophilic nature and primarily involves the adduction of protein thiols. The thiol glutathione (GSH) forms the first line of defense against acrolein. The present study confirms that acrolein added to isolated rat liver microsomes can increase microsomal GSH transferase (MGST) activity 2–3 fold, which can be seen as a direct adaptive increase in the protection against acrolein. At a relatively high exposure level, acrolein appeared to inhibit MGST. The activation is due to adduction of thiol groups, and the inactivation probably involves adduction of amino groups in the enzyme by acrolein. The preference of acrolein to react with thiol groups over amino groups can explain why the enzyme is activated at a low exposure level and inhibited at a high exposure level of acrolein. These opposite forms of direct adaptation on the level of enzyme activity further narrow the thin line between survival and promotion of cell death, governed by the level of exposure. Graphical abstract: Highlights: Exposure to acrolein first activates and then inhibits microsomal GSH S-transferase. It involves adduction of thiol (activation) or amino groups (inhibition) by acrolein. These adaptations narrow the thin line between survival and promotion of cell death.