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One-carbon cycle alterations induced by Dyrk1a dosage

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Hepatic dyrk1A protein expression, CBS activity, and plasma hcy levels in mice under-expressing Dyrk1a. (A) Dyrk1A protein expression was analyzed by slot blotting in the liver of wild type (WT) and mice under-expressing Dyrk1a (Dyrk1a (+/−)). (B) CBS activity in the liver of wild type (WT) and mice over-expressing Dyrk1a (Dyrk1a (+/−)). Data were normalized to the mean of wild-type (WT) mice. (C) Plasma hcy level. Data correspond to the medians with interquartile ranges. n = number of mice.
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f0005: Hepatic dyrk1A protein expression, CBS activity, and plasma hcy levels in mice under-expressing Dyrk1a. (A) Dyrk1A protein expression was analyzed by slot blotting in the liver of wild type (WT) and mice under-expressing Dyrk1a (Dyrk1a (+/−)). (B) CBS activity in the liver of wild type (WT) and mice over-expressing Dyrk1a (Dyrk1a (+/−)). Data were normalized to the mean of wild-type (WT) mice. (C) Plasma hcy level. Data correspond to the medians with interquartile ranges. n = number of mice.

Mentions: We first conducted the analysis of CBS activity in the liver of mice carrying only one copy of Dyrk1A, the Dyrk1a (+/−) mice [18]. The decreased protein expression of Dyrk1a (Fig. 1A), analyzed by slot blot method previously validated [23], was associated with a decreased CBS activity in liver of Dyrk1a (+/−) mice compared to control (wild type) mice (Fig. 1B). We observed a significant positive correlation between the liver CBS activity and liver Dyrk1A protein expression (ρ = 0.867, p < 0.009). Commensurate with the decreased hepatic CBS activity, plasma hcy levels were increased in Dyrk1a (+/−) mice compared to control (wild type) mice (Fig. 1C).


One-carbon cycle alterations induced by Dyrk1a dosage
Hepatic dyrk1A protein expression, CBS activity, and plasma hcy levels in mice under-expressing Dyrk1a. (A) Dyrk1A protein expression was analyzed by slot blotting in the liver of wild type (WT) and mice under-expressing Dyrk1a (Dyrk1a (+/−)). (B) CBS activity in the liver of wild type (WT) and mice over-expressing Dyrk1a (Dyrk1a (+/−)). Data were normalized to the mean of wild-type (WT) mice. (C) Plasma hcy level. Data correspond to the medians with interquartile ranges. n = number of mice.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5121348&req=5

f0005: Hepatic dyrk1A protein expression, CBS activity, and plasma hcy levels in mice under-expressing Dyrk1a. (A) Dyrk1A protein expression was analyzed by slot blotting in the liver of wild type (WT) and mice under-expressing Dyrk1a (Dyrk1a (+/−)). (B) CBS activity in the liver of wild type (WT) and mice over-expressing Dyrk1a (Dyrk1a (+/−)). Data were normalized to the mean of wild-type (WT) mice. (C) Plasma hcy level. Data correspond to the medians with interquartile ranges. n = number of mice.
Mentions: We first conducted the analysis of CBS activity in the liver of mice carrying only one copy of Dyrk1A, the Dyrk1a (+/−) mice [18]. The decreased protein expression of Dyrk1a (Fig. 1A), analyzed by slot blot method previously validated [23], was associated with a decreased CBS activity in liver of Dyrk1a (+/−) mice compared to control (wild type) mice (Fig. 1B). We observed a significant positive correlation between the liver CBS activity and liver Dyrk1A protein expression (ρ = 0.867, p < 0.009). Commensurate with the decreased hepatic CBS activity, plasma hcy levels were increased in Dyrk1a (+/−) mice compared to control (wild type) mice (Fig. 1C).

View Article: PubMed Central - PubMed

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.

No MeSH data available.