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One-carbon cycle alterations induced by Dyrk1a dosage

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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 GK and Wistar rats. (A) Dyrk1A protein expression was analyzed by slot blotting in the liver of Wistar (WT) and Goto-Kakizaki (GK) rats. (B) CBS activity in the liver of Wistar (WT) and Goto-Kakizaki (GK) rats. Data were normalized to the mean of Wistar (WT) rats. (C) Plasma hcy level. Data correspond to the medians with interquartile ranges. n = number of rats.
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f0015: Hepatic dyrk1A protein expression, CBS activity, and plasma hcy levels in GK and Wistar rats. (A) Dyrk1A protein expression was analyzed by slot blotting in the liver of Wistar (WT) and Goto-Kakizaki (GK) rats. (B) CBS activity in the liver of Wistar (WT) and Goto-Kakizaki (GK) rats. Data were normalized to the mean of Wistar (WT) rats. (C) Plasma hcy level. Data correspond to the medians with interquartile ranges. n = number of rats.

Mentions: We previously found a lower plasma level of hcy concomitantly with an increased liver activity of CBS in GK rats, a spontaneous nonobese model of type 2 diabetes [16]. We therefore used this rat model in order to analyze the hepatic Dyrk1a protein expression in a non-modified genetic context. The increased protein expression of Dyrk1a (Fig. 3A) was associated with an increased CBS activity in the liver of GK rats compared to nondiabetic Wistar (wild type) rats (Fig. 3B). We also observed a significant positive correlation between liver Dyrk1A protein expression and CBS activity (ρ = 0.625, p < 0.02). As previously described [15], plasma hcy levels were decreased in GK rats compared to Wistar (wild type) rats (Fig. 3C).


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

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

f0015: Hepatic dyrk1A protein expression, CBS activity, and plasma hcy levels in GK and Wistar rats. (A) Dyrk1A protein expression was analyzed by slot blotting in the liver of Wistar (WT) and Goto-Kakizaki (GK) rats. (B) CBS activity in the liver of Wistar (WT) and Goto-Kakizaki (GK) rats. Data were normalized to the mean of Wistar (WT) rats. (C) Plasma hcy level. Data correspond to the medians with interquartile ranges. n = number of rats.
Mentions: We previously found a lower plasma level of hcy concomitantly with an increased liver activity of CBS in GK rats, a spontaneous nonobese model of type 2 diabetes [16]. We therefore used this rat model in order to analyze the hepatic Dyrk1a protein expression in a non-modified genetic context. The increased protein expression of Dyrk1a (Fig. 3A) was associated with an increased CBS activity in the liver of GK rats compared to nondiabetic Wistar (wild type) rats (Fig. 3B). We also observed a significant positive correlation between liver Dyrk1A protein expression and CBS activity (ρ = 0.625, p < 0.02). As previously described [15], plasma hcy levels were decreased in GK rats compared to Wistar (wild type) rats (Fig. 3C).

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.