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Cystathionine Gamma‐Lyase Deficiency Impairs H2S Biosynthesis And Vessel Reactivity In Type‐2 Diabetes
Author(s) -
Velmurugan Gopal V,
White Carl
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1091.3
Subject(s) - cystathionine beta synthase , cystathionine gamma lyase , cysteine , endocrinology , vasodilation , chemistry , medicine , type 2 diabetes , diabetes mellitus , phenylephrine , nitric oxide , biosynthesis , biochemistry , enzyme , blood pressure
Together with the precursor L‐cysteine, cystathionine gamma‐lyase (CSE) is a key enzyme involved in the biosynthesis of hydrogen sulphide (H2S), a potent gaseous vasodilator. Since impaired vasodilation is a hallmark of diabetes the purpose of the current study was to assess the role of H2S in diabetes‐induced vascular dysfunction. Mesenteric arterioles from type‐2 diabetic (db/db) mice were found to express ~30% less CSE protein and 5 fold less CSE mRNA compared to nondiabetic (db/m) controls. In pressure myography experiments, addition of L‐cysteine (1 – 50 μM), to arterioles pre‐contracted with phenylephrine, dose‐dependently induced vasorelaxation in both db/m and db/db vessels, however, the efficacy of L‐cysteine was significantly lower in db/db. The CSE inhibitors D,L‐propargylglycine (PAG) and amino‐oxyacetic acid (AOAA) completely ablated L‐cysteine‐induced relaxation confirming that L‐cysteine operated through the H2S pathway. Incubating db/db vessels overnight with sulforaphane (500 nM), a phytochemical found in cruciferous vegetables, doubled its mRNA level. Taken together, these data suggest that reduced CSE expression and impaired H2S production may contribute to altered vascular reactivity in type‐2 diabetes and hint at the potential for sulforaphane to therapeutically correct H2S deficiency.