Aminooxyacetic acid up-regulates the Cry1 and Bmal1 clock gene in a sirtuin 1 dependent manner. In vitro study.

Abstract

The regulation of the cyclic oscillation of the components of the circadian clock is complex in itself. Numerous clock interactions with processes and molecules present in cells further complicate this mechanism. Recently, the anti-aging protein Silencing Information Regulator Two family member, SIRT1, has been linked with the molecular circadian clock. In this study, we investigated the in vitro effect of aminooxyacetic acid on SIRT1 expression in relation to circadian dynamics of Cry1 and Bma11 expressions in serum shocked NIH-3 T3 and HaCaT cells. The study was carried out in the context of the inhibitory activity of aminooxyacetic acid against cystathionine-β-synthase and cystathionine-γ-lyase. We have shown that aminooxyacetic acid effectively inhibits SIRT1 transcription and synthesis, which, given the pleiotropic effects of sirtuin 1 on numerous metabolic pathways, may have other implications. We also found that AOAA contributes to up-regulation of the expression of the Cry1 and Bmal1 genes in cells. This effect does not appear to be related to inhibition of the activity of cystathionine-β-synthase and cystathionine-γ-lyase. At the same time, this does not deny the role of hydrogen sulphide, a product of the activity of these enzymes, in the regulation of the circadian clock.