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Sex-specific dysregulation of cysteine oxidation and the methionine and folate cycles in female cystathionine gamma-lyase mice: a serendipitous model of the methylfolate trap.

Jiang H, Hurt KJ, Breen K, Stabler SP, Allen RH, Orlicky DJ, Maclean KN - Biol Open (2015)

Bottom Line: In addition to its role in the endogenous synthesis of cysteine, cystathionine gamma-lyase (CGL) is a major physiological source of the vasorelaxant hydrogen sulfide.Cgl mice of both sexes exhibited decreased expression of methylenetetrahydrofolate reductase and cysteinesulfinate decarboxylase compared to WT controls.Female Cgl mice exhibited a sex-specific induction of betaine homocysteine S-methyltransferase and methionine adenosyltransferase 1, alpha and a 70% decrease in methionine synthase expression accompanied by significantly decreased plasma methionine.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.

No MeSH data available.


Related in: MedlinePlus

Cgl  mice exhibit female-specific alteration of enzymes involved in the remethylation of methionine. Western blotting analysis of hepatic BHMT, MTHFR and MTR protein expression levels in male and female WT and Cgl  mice. Values shown represent the mean±s.d., *P<0.05, **P<0.01, ***P<0.001.
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BIO013433F4: Cgl mice exhibit female-specific alteration of enzymes involved in the remethylation of methionine. Western blotting analysis of hepatic BHMT, MTHFR and MTR protein expression levels in male and female WT and Cgl mice. Values shown represent the mean±s.d., *P<0.05, **P<0.01, ***P<0.001.

Mentions: To further characterize Hcy metabolism in Cgl mice, we examined the expression levels of BHMT, MTHFR and MTR in male and female WT and Cgl mice (Fig. 4). In this analysis, we observed a significant decrease in MTHFR protein levels in male and female Cgl mice relative to WT controls (P=0.048 and P=0.005 respectively). Previous work has shown that phosphorylation of the N-terminus of MTHFR results in increased catalytic activity and decreased sensitivity to the inhibitory effects of AdoMet (Yamada et al., 2005). The activated phosphorylated form of MTHFR can be resolved from the non-phosphorylated form by SDS-PAGE and we observed that both male and female Cgl mice exhibit a similar decrease in the level of phosphorylated MTHFR as a percentage of total MTHFR protein (Fig. 4).Fig. 4.


Sex-specific dysregulation of cysteine oxidation and the methionine and folate cycles in female cystathionine gamma-lyase mice: a serendipitous model of the methylfolate trap.

Jiang H, Hurt KJ, Breen K, Stabler SP, Allen RH, Orlicky DJ, Maclean KN - Biol Open (2015)

Cgl  mice exhibit female-specific alteration of enzymes involved in the remethylation of methionine. Western blotting analysis of hepatic BHMT, MTHFR and MTR protein expression levels in male and female WT and Cgl  mice. Values shown represent the mean±s.d., *P<0.05, **P<0.01, ***P<0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582125&req=5

BIO013433F4: Cgl mice exhibit female-specific alteration of enzymes involved in the remethylation of methionine. Western blotting analysis of hepatic BHMT, MTHFR and MTR protein expression levels in male and female WT and Cgl mice. Values shown represent the mean±s.d., *P<0.05, **P<0.01, ***P<0.001.
Mentions: To further characterize Hcy metabolism in Cgl mice, we examined the expression levels of BHMT, MTHFR and MTR in male and female WT and Cgl mice (Fig. 4). In this analysis, we observed a significant decrease in MTHFR protein levels in male and female Cgl mice relative to WT controls (P=0.048 and P=0.005 respectively). Previous work has shown that phosphorylation of the N-terminus of MTHFR results in increased catalytic activity and decreased sensitivity to the inhibitory effects of AdoMet (Yamada et al., 2005). The activated phosphorylated form of MTHFR can be resolved from the non-phosphorylated form by SDS-PAGE and we observed that both male and female Cgl mice exhibit a similar decrease in the level of phosphorylated MTHFR as a percentage of total MTHFR protein (Fig. 4).Fig. 4.

Bottom Line: In addition to its role in the endogenous synthesis of cysteine, cystathionine gamma-lyase (CGL) is a major physiological source of the vasorelaxant hydrogen sulfide.Cgl mice of both sexes exhibited decreased expression of methylenetetrahydrofolate reductase and cysteinesulfinate decarboxylase compared to WT controls.Female Cgl mice exhibited a sex-specific induction of betaine homocysteine S-methyltransferase and methionine adenosyltransferase 1, alpha and a 70% decrease in methionine synthase expression accompanied by significantly decreased plasma methionine.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.

No MeSH data available.


Related in: MedlinePlus