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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

BHMT activity is increased in Cgl  mice. (A) Hepatic BHMT activity in WT control and male and female Cgl  mice was determined as described in the Materials and Methods. As there was no significant difference in BHMT activity between male and female WT mice values derived from both sexes were combined and represent an n of 12.Values shown for Cgl  mice represent the mean±s.d. derived from an n of 6 for each group. (B) Cgl  female but not male mice exhibit significantly reduced levels of plasma methionine. Plasma levels of methionine in wild type (WT) mice plus and minus treatment with the CGL specific inhibitor PPG and untreated male and female Cgl  mice. Values shown represent the mean±s.d. derived from 20 animals for WT and 10 animals for all other groups. ***P<0.001.
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BIO013433F5: BHMT activity is increased in Cgl mice. (A) Hepatic BHMT activity in WT control and male and female Cgl mice was determined as described in the Materials and Methods. As there was no significant difference in BHMT activity between male and female WT mice values derived from both sexes were combined and represent an n of 12.Values shown for Cgl mice represent the mean±s.d. derived from an n of 6 for each group. (B) Cgl female but not male mice exhibit significantly reduced levels of plasma methionine. Plasma levels of methionine in wild type (WT) mice plus and minus treatment with the CGL specific inhibitor PPG and untreated male and female Cgl mice. Values shown represent the mean±s.d. derived from 20 animals for WT and 10 animals for all other groups. ***P<0.001.

Mentions: BHMT protein levels were unchanged in male Cgl mice but were increased by approximately 30% in female Cgl mice relative to WT controls (P=0.0003) (Fig. 4) suggesting a possible induction by elevated tHcy. This induction was subsequently confirmed by BHMT activity assays performed using liver extracts as described in the Materials and Methods section (Fig. 5A). This analysis observed a 40% and two-fold induction of BHMT activity in male and female Cgl mice respectively (P=0.0006 and P=0.0039 respectively).Fig. 5.


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)

BHMT activity is increased in Cgl  mice. (A) Hepatic BHMT activity in WT control and male and female Cgl  mice was determined as described in the Materials and Methods. As there was no significant difference in BHMT activity between male and female WT mice values derived from both sexes were combined and represent an n of 12.Values shown for Cgl  mice represent the mean±s.d. derived from an n of 6 for each group. (B) Cgl  female but not male mice exhibit significantly reduced levels of plasma methionine. Plasma levels of methionine in wild type (WT) mice plus and minus treatment with the CGL specific inhibitor PPG and untreated male and female Cgl  mice. Values shown represent the mean±s.d. derived from 20 animals for WT and 10 animals for all other groups. ***P<0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

BIO013433F5: BHMT activity is increased in Cgl mice. (A) Hepatic BHMT activity in WT control and male and female Cgl mice was determined as described in the Materials and Methods. As there was no significant difference in BHMT activity between male and female WT mice values derived from both sexes were combined and represent an n of 12.Values shown for Cgl mice represent the mean±s.d. derived from an n of 6 for each group. (B) Cgl female but not male mice exhibit significantly reduced levels of plasma methionine. Plasma levels of methionine in wild type (WT) mice plus and minus treatment with the CGL specific inhibitor PPG and untreated male and female Cgl mice. Values shown represent the mean±s.d. derived from 20 animals for WT and 10 animals for all other groups. ***P<0.001.
Mentions: BHMT protein levels were unchanged in male Cgl mice but were increased by approximately 30% in female Cgl mice relative to WT controls (P=0.0003) (Fig. 4) suggesting a possible induction by elevated tHcy. This induction was subsequently confirmed by BHMT activity assays performed using liver extracts as described in the Materials and Methods section (Fig. 5A). This analysis observed a 40% and two-fold induction of BHMT activity in male and female Cgl mice respectively (P=0.0006 and P=0.0039 respectively).Fig. 5.

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