Aldehyde dehydrogenases may modulate signaling by lipid peroxidation-derived bioactive aldehydes

Aldehyde molecules were shown to induce gene expression but because of their toxicity, the cell expresses ALDEHYDE DEHYDROGENASES (ALDH, EC 1.2.1.3) that oxidize them to carboxylic acids. To understand how the aldehydes may be both toxic and gene activators, we expressed the ALDH7B4 gene promoter fused to the β-glucuronidase reporter gene in independent transgenic lines and found that pentanal and trans-2-hexenal activated the promoter whereas trans-2-hexenal induced the ALDH7B4 protein. Paraquat led to higher amounts of malondialdehyde compared to trans-2-hexenal and H₂O₂, and only the treatment by Paraquat activated the ALDH7B4 promoter, indicating that a threshold level of aldehydes is required for gene activation. These findings suggest that ALDH activity may also serve to fine-tune gene activation by the aldehydes.