Dyrk1a activates antioxidant NQO1 expression through an ERK12-Nrf2 dependent mechanism.
Among cardiovascular risk factor, people with Down syndrome have a lower plasma homocysteine level. In a previous study, we have shown that DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a), a serinethreonine kinase found on human chromosome 21, is implicated on homocysteine metabolism regulation. Indeed, mice that overexpress in liver this kinase have a lower plasma homocysteine level concomitant with an increased hepatic S-adenosyhomocysteine hydrolase (SAHH) activity, which depends on the activation of NAD(P)Hquinone oxidoreductase-1 (NQO1). Since NQO1 gene transcription is under the control of NRF2 and AhR, the aim of the present study was to analyze the effect of DYRK1A overexpression in mice onto NRF2 and AhR signaling pathways. Effects of DYRK1A overexpression were examined in mice overexpressing Dyrk1a treated with an inhibitor, harmine, by real-time quantitative reverse-transcription polymerase reaction and western blotting. We found that overexpression of DYRK1A increases the nuclear NRF2 quantity, concomitant with the activation of ERK12. We also show that the overexpression of Dyrk1a has no effect on PI3KAKT activation, and AhR signaling pathway in liver of mice. Our results reveal a link between DYRK1A and NRF2 signaling pathway.