title: Dyrk1a activates antioxidant NQO1 expression through an ERK1/2-Nrf2 dependent mechanism.
abstract: OBJECTIVE
  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.
authors.affiliation: Univ Paris Diderot-CNRS EAC 4413, Unit of Functional and Adaptive Biology (BFA), Case 7104, 75205 Paris cedex 13, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Noll
authors.forename: Asma
authors.initials: A
authors.lastname: Tlili
authors.forename: Clémentine
authors.initials: C
authors.lastname: Ripoll
authors.forename: Ludovic
authors.initials: L
authors.lastname: Mallet
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Paul
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Delabar
authors.forename: Nathalie
authors.initials: N
authors.lastname: Janel
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D005260:Female; D006247:Harmine / Q000494:pharmacology; D006710:Homocysteine / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D000097603:Dyrk Kinases
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D006247:Harmine; D006710:Homocysteine; D020928:Mitogen-Activated Protein Kinases; D016660:NAD(P)H Dehydrogenase (Quinone); D051267:NF-E2-Related Factor 2; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D018336:Receptors, Aryl Hydrocarbon; D000097603:Dyrk Kinases; C484722:Ahr protein, mouse; C491732:Nqo1 protein, mouse