Nitric oxide (NO) has been shown as an important signaling messenger involved in cardioprotection of ischemic preconditioning (IPC). To date, most studies suggest that NO might provide its protective effects by regulating the mitochondrial
ATP-sensitive
potassium (K(
ATP)) channel via the classic NO/cGMP-dependent pathway. However, there is emerging data suggesting that NO might also elicit its physiological role through
protein S-nitrosylation.
Protein S-nitrosylation, the covalent attachment of an NO moiety to sulfhydryl group(s) of
cysteine residue(s) of
proteins, is a reversible post-translational protein modification involved in redox-based cellular signaling. IPC has been found to increase
S-nitrosothiol content and result in increased S-nitrosylation of
proteins, which not only induces the structural and functional changes of modified
proteins, but also prevents the target
cysteine residue(s) from the further oxidative modification. In addition,
S-nitrosothiols could elicit pharmacological preconditioning effect and protect against
myocardial ischemia-
reperfusion injury. Thus,
protein S-nitrosylation is emerging as an important contributor to cardioprotection in IPC, providing protection from cellular oxidative and nitrosative stress.