Modification of cell constituents with endogenous aldehydes and its biological significance

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Aldehydes which exist in the living system are capable of chemically modifying cell constituents such as protein. The object of this project is focused on the effect of aldehydes on the gene expressions which are induced by DNA lesions such as methylation and oxidative stresses. First, effect on umuDC and ada gene expressions were examined. The gene expressions were monitored by measuring beta-galactosidase activity from umuDC'-'lacZ and ada'-'lacZ fused genes, respectively, in E. coli. Among aldehydes examined, formaldehyde slightly suppressed the expression of ada gene, which encodes DNA repair enzyme, O^6-methyguanine-DNA methyltransferase, induced by methylating agents. Formaldehyde did not affect constitutive level of the ada gene expression in the absence of methylating agents. It is known that cells which are unable to induce ada gene expression are hypersensitive to methylating agents. It may, therefore, be expected that formaldehyde potentiates mutagenicity of methylating agents. Second, the effect of aldehydes on the gene expressions induced by metal ions which are known to produce active oxygen species was examined. Metal ions such as Cd^<2+> and Hg^<2+> showed suppressive effect on the ada gene expression induced by methylating agents. The results obtained from the experiment using in vitro reconstituted system indicated that these metals probably bound to Ada protein leading to inhibition of transcriptional promoting activity of Ada protein.