Τίτλος:
Cardiovascular phenotype of mice lacking 3-mercaptopyruvate sulfurtransferase
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Rationale: Hydrogen sulfide (H2S) is a physiological mediator that regulates cardiovascular homeostasis. Three major enzymes contribute to the generation of endogenously produced H2S, namely cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). Although the biological roles of CSE and CBS have been extensively investigated in the cardiovascular system, very little is known about that of 3-MST. In the present study we determined the importance of 3-MST in the heart and blood vessels, using a genetic model with a global 3-MST deletion. Results: 3-MST is the most abundant transcript in the mouse heart, compared to CSE and CBS. 3-MST was mainly localized in smooth muscle cells and cardiomyocytes, where it was present in both the mitochondria and the cytosol. Levels of serum and cardiac H2S species were not altered in adult young (2–3 months old) 3-MST−/− mice compared to WT animals. No significant changes in the expression of CSE and CBS were observed. Additionally, 3-MST−/− mice had normal left ventricular structure and function, blood pressure and vascular reactivity. Interestingly, genetic ablation of 3-MST protected mice against myocardial ischemia reperfusion injury, and abolished the protection offered by ischemic pre- and post-conditioning. 3-MST−/− mice showed lower expression levels of thiosulfate sulfurtransferase, lower levels of cellular antioxidants and elevated basal levels of cardiac reactive oxygen species. In parallel, 3-MST−/− mice showed no significant alterations in endothelial NO synthase or downstream targets. Finally, in a separate cohort of older 3-MST−/− mice (18 months old), a hypertensive phenotype associated with cardiac hypertrophy and NO insufficiency was observed. Conclusions: Overall, genetic ablation of 3-MST impacts on the mouse cardiovascular system in an age-dependent manner. Loss of 3-MST exerts a cardioprotective role in young adult mice, while with aging it predisposes them to hypertension and cardiac hypertrophy. © 2020 Elsevier Inc.
Συγγραφείς:
Peleli, M.
Bibli, S.-I.
Li, Z.
Chatzianastasiou, A.
Varela, A.
Katsouda, A.
Zukunft, S.
Bucci, M.
Vellecco, V.
Davos, C.H.
Nagahara, N.
Cirino, G.
Fleming, I.
Lefer, D.J.
Papapetropoulos, A.
Περιοδικό:
Biochemical Pharmacology
Εκδότης:
ELSEVIER SCIENCE INC 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
Λέξεις-κλειδιά:
3 mercaptopyruvate sulfurtransferase; antioxidant; cystathionine beta synthase; cystathionine gamma lyase; endothelial nitric oxide synthase; hydrogen sulfide; nitric oxide; reactive oxygen metabolite; superoxide; thiosulfate sulfurtransferase; 3-mercaptopyruvate sulphurtransferase; antioxidant; cystathionine beta synthase; cystathionine gamma lyase; hydrogen sulfide; nitric oxide; reactive oxygen metabolite; sulfurtransferase, adult; age; aging; animal experiment; animal model; animal tissue; Article; blood pressure; blood vessel; blood vessel reactivity; cardiac muscle cell; cardiovascular function; cardiovascular system; cell level; controlled study; cytosol; echocardiography; elevated blood pressure; gene deletion; gene expression; genetic model; heart left ventricle function; heart mitochondrion; heart protection; heart ventricle hypertrophy; heart weight; hypertension; ischemic postconditioning; ischemic preconditioning; male; morphology; mouse; myocardial ischemia reperfusion injury; nonhuman; oxidative stress; phenotype; priority journal; protein blood level; protein expression; protein function; smooth muscle cell; young adult; animal; blood; C57BL mouse; cardiovascular system; drug effect; enzymology; gene expression regulation; genetics; knockout mouse; metabolism; phenotype; vasodilatation, Animals; Antioxidants; Cardiovascular System; Cystathionine beta-Synthase; Cystathionine gamma-Lyase; Gene Expression Regulation, Enzymologic; Hydrogen Sulfide; Male; Mice, Inbred C57BL; Mice, Knockout; Myocardial Reperfusion Injury; Myocytes, Cardiac; Nitric Oxide; Phenotype; Reactive Oxygen Species; Sulfurtransferases; Vasodilation
DOI:
10.1016/j.bcp.2020.113833
