Regulation of polyamine metabolism

Biogenic polyamines spermine and spermidine are the oligocations that are present in cells at high concentrations and that regulate cell growth and differentiation. Polyamine concentrations are carefully maintained by coordinated control over the enzymes of their biosynthesis and catabolism. However, mechanisms of regulation of several key polyamine-metabolizing enzymes remain poorly studied.

We previously described that ornithine decarboxylase (ODC) and spermidine/spermine-N1-acetyltransferase (SSAT) are regulated by the redox-sensitive Nrf2 transcription factor, thus linking this metabolic system with oxidative stress (Smirnova et al, Biochimie 2012). This mechanism account for transient induction of these enzymes during hepatitis C virus infection (Smirnova et al, BBRC 2017).

Spermine oxidase (SMO/SMOX) and acetylpolyamine oxidase (APAO/PAOX) are the perspective goals for the development of antiviral agents, as our data indicate that their inhibitor MDL72.527 displays antiviral activity towards RNA viruses (Patent RU2667123C1 -2018; Patent RU2761565C1 – 2020). Moreover, this compounds was shown to overcome resistance of leukemia cells to anticancer agent doxorubicin, conferred by human cytomegalovirus (Fedorova et al, Biochimie 2019).

APAO is considered a peroxisomal enzyme that is transiently expressed and that catalyzes a non-rate-limiting step of polyamine catabolism. However, transcription rates of its gene in multiple cell lines remain very low. So, our current activities are focused on analysis of principles of APAO expression in human cells and re-evaluation of role of this enzyme in polyamine homeostasis.