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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

Sex-specific alterations in cysteine metabolism in Cgl  mice. (A) Cgl  female but not male mice exhibit significantly reduced levels of plasma cysteine. Plasma levels of cysteine in wild type (WT) mice plus and minus treatment with the CGL specific inhibitor PPG and untreated male and female Cgl  mice. n=10. (B,C) Male and female Cgl  mice exhibit sex-specific alterations in cysteine oxidation. Western blotting analysis and protein expression levels of hepatic CDO and CSAD (B) and GOT1 and GOT2 (C) 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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BIO013433F6: Sex-specific alterations in cysteine metabolism in Cgl mice. (A) Cgl female but not male mice exhibit significantly reduced levels of plasma cysteine. Plasma levels of cysteine in wild type (WT) mice plus and minus treatment with the CGL specific inhibitor PPG and untreated male and female Cgl mice. n=10. (B,C) Male and female Cgl mice exhibit sex-specific alterations in cysteine oxidation. Western blotting analysis and protein expression levels of hepatic CDO and CSAD (B) and GOT1 and GOT2 (C) 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: We determined the plasma levels of cysteine in male and female WT mice plus and minus PPG treatment and male and female Cgl mice. Male Cgl mice showed essentially identical tCys levels compared to both male and female WT controls irrespective of PPG treatment (Fig. 6A). Interestingly, female Cgl mice exhibited significantly lower plasma tCys compared to WT control mice plus or minus PPG (P=0.001) and Cgl male mice indicating that plasma levels of this compound are significantly lowered as a consequence of severely elevated tHcy rather than as a consequence of blocked endogenous synthesis.Fig. 6.


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)

Sex-specific alterations in cysteine metabolism in Cgl  mice. (A) Cgl  female but not male mice exhibit significantly reduced levels of plasma cysteine. Plasma levels of cysteine in wild type (WT) mice plus and minus treatment with the CGL specific inhibitor PPG and untreated male and female Cgl  mice. n=10. (B,C) Male and female Cgl  mice exhibit sex-specific alterations in cysteine oxidation. Western blotting analysis and protein expression levels of hepatic CDO and CSAD (B) and GOT1 and GOT2 (C) 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

BIO013433F6: Sex-specific alterations in cysteine metabolism in Cgl mice. (A) Cgl female but not male mice exhibit significantly reduced levels of plasma cysteine. Plasma levels of cysteine in wild type (WT) mice plus and minus treatment with the CGL specific inhibitor PPG and untreated male and female Cgl mice. n=10. (B,C) Male and female Cgl mice exhibit sex-specific alterations in cysteine oxidation. Western blotting analysis and protein expression levels of hepatic CDO and CSAD (B) and GOT1 and GOT2 (C) 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: We determined the plasma levels of cysteine in male and female WT mice plus and minus PPG treatment and male and female Cgl mice. Male Cgl mice showed essentially identical tCys levels compared to both male and female WT controls irrespective of PPG treatment (Fig. 6A). Interestingly, female Cgl mice exhibited significantly lower plasma tCys compared to WT control mice plus or minus PPG (P=0.001) and Cgl male mice indicating that plasma levels of this compound are significantly lowered as a consequence of severely elevated tHcy rather than as a consequence of blocked endogenous synthesis.Fig. 6.

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