Τίτλος:
Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban pathway
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Aims: H2S is known to confer cardioprotection; however, the pathways mediating its effects in vivo remain incompletely understood. The purpose of the present study is to evaluate the contribution of cGMP-regulated pathways in the infarct-limiting effect of H2S in vivo. Methods and results: Anaesthetized rabbits were subjected to myocardial ischaemia (I)/reperfusion (R), and infarct size was determined in control or H2S-exposed groups. The H2S donor sodium hydrosulfide (NaHS, an agent that generates H2S) increased cardiac cGMP and reduced the infarct size. The cGMP-dependent protein kinase (PKG)-I inhibitor DT2 abrogated the protective effect of NaHS, whereas the control peptide TAT or l-nitroarginine methyl ester (l-NAME) did not alter the effect of NaHS. Moreover, the KATP channel inhibitor, glibenclamide, partially reversed the effects of NaHS, whereas inhibition of mitochondrial KATP did not modify the NaHS response. NaHS enhanced phosphorylation of phospholamban (PLN), in a PKG-dependent manner. To further investigate the role of PLN in H2S-mediated cardioprotection, wild-type and PLN KO mice underwent I/R. NaHS did not exert cardioprotection in PLN KO mice. Unlike what was observed in rabbits, genetic or pharmacological inhibition of eNOS abolished the infarct-limiting effect of NaHS in mice. Conclusions: Our findings demonstrate (i) that administration of NaHS induces cardioprotection via a cGMP/PKG/PLN pathway and (ii) contribution of nitric oxide to the H2S response is species-specific. © 2015 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015.
Συγγραφείς:
Bibli, S.-I.
Andreadou, I.
Chatzianastasiou, A.
Tzimas, C.
Sanoudou, D.
Kranias, E.
Brouckaert, P.
Coletta, C.
Szabo, C.
Kremastinos, D.T.
Iliodromitis, E.K.
Papapetropoulos, A.
Περιοδικό:
Cardiovascular Research
Εκδότης:
Oxford University Press
Λέξεις-κλειδιά:
adenosine triphosphate; cyclic GMP; cyclic GMP dependent protein kinase; endothelial nitric oxide synthase; hydrogen sulfide; phospholamban; calcium binding protein; cyclic GMP; cyclic GMP dependent protein kinase; endothelial nitric oxide synthase; hydrogen sulfide; nitric oxide; Nos3 protein, mouse; phospholamban; protein kinase inhibitor; sodium bisulfide; sulfide, animal experiment; animal model; Article; controlled study; enzyme inhibition; female; heart infarction size; heart muscle ischemia; heart protection; in vivo study; male; mouse; nonhuman; priority journal; protein phosphorylation; animal; antagonists and inhibitors; C57BL mouse; cardiac muscle cell; deficiency; disease model; drug effects; enzyme activation; enzymology; genetics; knockout mouse; metabolism; Myocardial Infarction; Myocardial Reperfusion Injury; pathology; phosphorylation; rabbit; signal transduction; species difference, Animals; Calcium-Binding Proteins; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Disease Models, Animal; Enzyme Activation; Female; Hydrogen Sulfide; Male; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Nitric Oxide; Nitric Oxide Synthase Type III; Phosphorylation; Protein Kinase Inhibitors; Rabbits; Signal Transduction; Species Specificity; Sulfides
