title: One-carbon cycle alterations induced by Dyrk1a dosage.
abstract: Hyperhomocysteinemia due to cystathionine beta synthase deficiency confers diverse clinical manifestations. It is characterized by elevated plasma homocysteine levels, a common amino acid metabolized by remethylation to methionine or transsulfuration to cysteine. We recently found a relationship between hepatic Dyrk1A protein expression, a serine/threonine kinase involved in signal transduction in biological processes, hepatic S-adenosylhomocysteine activity, and plasma homocysteine levels. We aimed to study whether there is also a relationship between Dyrk1a and cystathionine beta synthase activity. We used different murine models carrying altered gene coy numbers for Dyrk1a, and found a decreased cystathionine beta synthase activity in the liver of mice under-expressing Dyrk1a, and an increased in liver of mice over-expressing Dyrk1a. For each model, a positive correlation was found between cystathionine beta synthase activity and Dyrk1a protein expression in the liver of mice, which was confirmed in a non-modified genetic context. The positive correlation found between liver Dyrk1a protein expression and CBS activity in modified and non-modified genetic context strengthens the role of this kinase in one carbon metabolism.
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 CNRS, F-75205 Paris, France.
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Delabar
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 CNRS, F-75205 Paris, France.
authors.forename: Alizée
authors.initials: A
authors.lastname: Latour
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 CNRS, F-75205 Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Noll
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 CNRS, F-75205 Paris, France.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Renon
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 CNRS, F-75205 Paris, France.
authors.forename: Sacha
authors.initials: S
authors.lastname: Salameh
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Service de Biochimie, 75015 Paris, France; Univ Paris-Sud, EA 4529, UFR de Pharmacie, 92296 Châtenay-Malabry, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Paul
authors.affiliation: Instituto de Biología Molecular de Barcelona (CSIC), Barcelona, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Arbones
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 CNRS, F-75205 Paris, France.
authors.forename: Jamileh
authors.initials: J
authors.lastname: Movassat
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 CNRS, F-75205 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Janel
keywords: CBS, cystathionine beta synthase; Cystathionine beta synthase; DS, Down syndrome; DYRK, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase; Dyrk1a; EGCG, epigallocatechin-gallate; GABA, gamma-amino-butyric-acid; GK, Goto-Kakizaki; Homocysteine; Liver; Murine model; NQO1, NAD(P)H:quinone oxidoreductase; PLP, pyridoxal phosphate; PTZ, pentylenetetrazole; SAH, S-adenosylhomocysteine; SAHH, SAH hydrolase; hcy, homocysteine