2P-33 PDF
Elucidation of the intracellular detoxication mechanism of α, β-unsaturated carbonyl compounds using LC/MS analysis
Aqueous cigarette smoke extract (CSE) contains many oxidants which can cause injury to various cells. We have previously detected methyl vinyl ketone (MVK), an α, β-unsaturated ketone, as an active ingredient in CSE, and also showed that MVK as well as CSE irreversibly modifies glutathione (GSH), an important antioxidant, in mouse melanoma cells, resulting in its rapid depletion. In addition, we have found that other reactive and toxic α, β-unsaturated aldehydes present in CSE, such as acrolein (ACR) and crotonaldehyde (CA), similarly react with GSH to form conjugates, which are further reduced to alcohols by aldose reductase in the cell. The mass spectral peaks at m/z 380 and m/z 366 corresponding to the mass of their alcohols were not detected when the cell were absent3).
In this study, we measured the intracellular and extracellular concentration of the conjugates with GSH and their reduced form (alcohols) to elucidate the cellular metabolism of the GSH conjugates of α, β-unsaturated carbonyl compounds, MVK, ACR and CA.