Activation versus inhibition of microsomal glutathione S-transferase activity by acrolein. Dependence on the concentration and time of acrolein exposure

Chem Biol Interact. 2017 Sep 25;275:116-120. doi: 10.1016/j.cbi.2017.08.001. Epub 2017 Aug 2.

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.

Keywords: Acrolein; Adaptation; Glutathione; Microsomal GSH S-transferase.

MeSH terms

  • Acrolein / chemistry
  • Acrolein / metabolism
  • Acrolein / pharmacology*
  • Animals
  • Enzyme Activation / drug effects
  • Enzyme Activators / pharmacology
  • Enzyme Assays
  • Enzyme Inhibitors / pharmacology
  • Glutathione / chemistry
  • Glutathione / metabolism
  • Glutathione Transferase / chemistry
  • Glutathione Transferase / metabolism*
  • Kinetics
  • Male
  • Microsomes, Liver / enzymology*
  • Ninhydrin / chemistry
  • Ninhydrin / metabolism
  • Rats
  • Rats, Wistar
  • Spectrophotometry, Ultraviolet
  • Time Factors

Substances

  • Enzyme Activators
  • Enzyme Inhibitors
  • Acrolein
  • Glutathione Transferase
  • Glutathione
  • Ninhydrin