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What is the role of S‐nitrosation of soluble guanylyl cyclase in the heart? (698.9)
Author(s) -
Huang Can,
Crassous PierreAntoine,
Beuve Annie
Publication year - 2014
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.28.1_supplement.698.9
Subject(s) - soluble guanylyl cyclase , cardioprotection , chemistry , nitric oxide , s nitrosylation , microbiology and biotechnology , protein subunit , sarcolemma , cytosol , desmin , cgmp dependent protein kinase , peroxynitrite , biochemistry , myocyte , protein kinase a , kinase , guanylate cyclase , cysteine , biology , medicine , ischemia , superoxide , enzyme , mitogen activated protein kinase kinase , immunohistochemistry , vimentin , organic chemistry , gene
Nitric oxide (NO) is involved in cardioprotection against ischemia/reperfusion (I/R) injury. Soluble guanylyl cyclase (sGC) produces cGMP when it is stimulated by NO. Association of the α and β subunit of sGC is required for cGMP‐forming activity. NO protects the heart from I/R via a cGMP‐dependent and a S‐nitrosation (SNO)‐dependent pathway. Preliminary evidence showed that sGC‐overexpression increases S‐nitrosation of specific proteins (SNO‐proteins) in rat neonatal cardiomyocytes. These sGC‐dependent SNO‐proteins were identified by Mass Spectrometry and are mostly associated with intercalated disc and cytoskeleton, including integrin‐linked kinase (ILK) and desmin. sGC is heavily S‐nitrosated in the presence of nitrosating agent. Thus, we hypothesize that sGC acts as a transnitrosylase in the heart, e.g. transfers its SNO to specific proteins. Intriguingly, sGC‐α and β subunits localize differently in cardiomyocytes. β is at the nuclear envelope and sarcolemma, while α is in cytosol, suggesting that each subunit might have a separate function, independent of cGMP‐forming activity. In cardiomyocytes treated with a nitrosating agent, overexpressing a single sGC subunit, either α or β, was sufficient to increase SNO level of ILK and desmin. Hence, we propose that sGC could modulate cardioprotection by increasing protein‐SNO, in addition to the NO‐cGMP dependent pathway. Grant Funding Source : Supported by 6R01 GM067640