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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

Severely elevated Hcy does not induce CBS or SAHH expression in female Cgl  mice. Western blotting analysis of hepatic SAHH, CBS and CGL protein expression levels in male and female WT and Cgl  mice. Blotting and immunostaining were performed as described in the Materials and Methods section, In this experiment and all subsequent blots, the relative intensities of protein bands were quantified using Quantity One version 4.6.5 software (Bio Rad). Signal intensity from target bands were calculated relative to GAPDH signal intensity. All blots shown are representative of a minimum of two independent experiments. Values shown represent the mean±s.d., *P<0.05.
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BIO013433F2: Severely elevated Hcy does not induce CBS or SAHH expression in female Cgl mice. Western blotting analysis of hepatic SAHH, CBS and CGL protein expression levels in male and female WT and Cgl mice. Blotting and immunostaining were performed as described in the Materials and Methods section, In this experiment and all subsequent blots, the relative intensities of protein bands were quantified using Quantity One version 4.6.5 software (Bio Rad). Signal intensity from target bands were calculated relative to GAPDH signal intensity. All blots shown are representative of a minimum of two independent experiments. Values shown represent the mean±s.d., *P<0.05.

Mentions: As expected, we observed no trace of CGL protein in either male or female Cgl mice (Fig. 2). This finding was subsequently confirmed by enzyme assay which found no detectable CGL activity confirming that our findings are not an artifact of erroneous genotyping. No significant increase in CBS protein was observed compared to WT controls in either female or male Cgl mice (Fig. 2) indicating that this enzyme is not induced by elevated tHcy in either male or female Cgl mice. Consistent with the western blotting analysis, enzyme assays found no significant difference in hepatic CBS activity between male and female WT and Cgl mice (data not shown). Collectively, these results are consistent with the absence of any significant difference in plasma cystathionine between male and female Cgl mice described above.Fig. 2.


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)

Severely elevated Hcy does not induce CBS or SAHH expression in female Cgl  mice. Western blotting analysis of hepatic SAHH, CBS and CGL protein expression levels in male and female WT and Cgl  mice. Blotting and immunostaining were performed as described in the Materials and Methods section, In this experiment and all subsequent blots, the relative intensities of protein bands were quantified using Quantity One version 4.6.5 software (Bio Rad). Signal intensity from target bands were calculated relative to GAPDH signal intensity. All blots shown are representative of a minimum of two independent experiments. Values shown represent the mean±s.d., *P<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

BIO013433F2: Severely elevated Hcy does not induce CBS or SAHH expression in female Cgl mice. Western blotting analysis of hepatic SAHH, CBS and CGL protein expression levels in male and female WT and Cgl mice. Blotting and immunostaining were performed as described in the Materials and Methods section, In this experiment and all subsequent blots, the relative intensities of protein bands were quantified using Quantity One version 4.6.5 software (Bio Rad). Signal intensity from target bands were calculated relative to GAPDH signal intensity. All blots shown are representative of a minimum of two independent experiments. Values shown represent the mean±s.d., *P<0.05.
Mentions: As expected, we observed no trace of CGL protein in either male or female Cgl mice (Fig. 2). This finding was subsequently confirmed by enzyme assay which found no detectable CGL activity confirming that our findings are not an artifact of erroneous genotyping. No significant increase in CBS protein was observed compared to WT controls in either female or male Cgl mice (Fig. 2) indicating that this enzyme is not induced by elevated tHcy in either male or female Cgl mice. Consistent with the western blotting analysis, enzyme assays found no significant difference in hepatic CBS activity between male and female WT and Cgl mice (data not shown). Collectively, these results are consistent with the absence of any significant difference in plasma cystathionine between male and female Cgl mice described above.Fig. 2.

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