Dyrk1a activates antioxidant NQO1 expression through an ERK1/2-Nrf2 dependent mechanism

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• 作者：Christophe Noll^a ; Asma Tlili^a ; Clé ; mentine Ripoll^a ; Ludovic Mallet^b ; Jean-Louis Paul^c ; ^d ; Jean-Maurice Delabar^a ; Nathalie Janel^a ; ^{janel@univ-paris-diderot.fr}
• 关键词：DYRK1A ; dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a ; SAHH ; S-adenosylhomocysteine hydrolase ; NQO1 ; NAD(P)H ; quinone oxidoreductase-1 ; Hcy ; homocysteine ; SAM ; S-adenosylmethionine ; SAH ; S-adenosylhomocysteine ; CBS ; cystathionine beta s
• 刊名：Molecular Genetics and Metabolism
• 出版年：2012
• 期刊代码：175_10967192
• 类别：bio
• 出版时间：March, 2012
• 卷：105
• 期：3
• 页码：484-488
• 文件大小：367 K

摘要

Background and aims

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 serine/threonine 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)H:quinone 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.

Methods

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.

Results

We found that overexpression of DYRK1A increases the nuclear NRF2 quantity, concomitant with the activation of ERK1/2. We also show that the overexpression of Dyrk1a has no effect on PI3K/AKT activation, and AhR signaling pathway in liver of mice.

Conclusions

Our results reveal a link between DYRK1A and NRF2 signaling pathway.