Toxicity of derivatives from semicarbazide-sensitive amine oxidase-mediated deamination of methylamine against Toxoplasma gondii after infection of differentiated 3T3-L1 cells.

ABSTRACT

Adipose tissue plays an active role in normal metabolic homeostasis as well as in the development of human diseases such as atherosclerosis and diabetes. We report here antimicrobial activities of the metabolites from adipocytes. Specifically, semicarbazide-sensitive amine oxidase of differentiated 3T3-L1 cells was found to utilize methylamine for producing formaldehyde and hydrogen peroxide, accounting for the inhibition of infectivity of Toxoplasma gondii and its replication in these cells. This was demonstrated by the findings that semicarbazide-sensitive amine oxidase was extremely high in differentiated 3T3-L1 cells; and that the infection of these cells by T. gondii and its intracellular replication were decreased to 33% and 37% of the control, respectively, when methylamine was provided in micromolar concentrations as the substrate to the aminoxidase. Only one of the two reaction products expected was found inhibitory against T. gondii when added to the infected pre-adipocytes of 3T3-L1. Intracellular replication of this parasite was inhibited by formaldehyde in the range of 10-100 microM and stimulated by hydrogen peroxide at 1-10 microM. The finding indicates that T. gondii may be useful as a sensitive and convenient sentinel for screening agents toxic to eukaryotic cells.