Pharmacological postconditioning against myocardial infarction with a slow-releasing hydrogen sulfide donor, GYY4137

Abstract

36Exogenous hydrogen sulfide (H 2 S) protects against myocardial ischemia/reperfusion 37 injury but the mechanism of action is unclear. The present study investigated the 38 effect of GYY4137, a slow-releasing H 2 S donor, on myocardial infarction given 39 specifically at reperfusion and the signalling pathway involved.

AP39, a mitochondria-targeting hydrogen sulfide (H2S) donor, protects against myocardial reperfusion injury independently of salvage kinase signalling

“…It is noteworthy that the optimum cardioprotective doses of GYY4137 and AP39 used were 26.6 and 0.25 μmol·kg −1 respectively. Very recently, we reported that 26.6 μmol·kg −1 GYY4137 was not cardioprotective in an in vivo rat model of ischaemia/reperfusion injury with the optimum cardioprotective dose being 10‐fold higher (Karwi et al ., ). Similarly, in the present study, we demonstrated that AP39 exerts an infarct‐sparing effect with an optimum cardioprotective dose of 1 μmol·kg −1 , fourfold higher than the effective dose in mouse reported by Chatzianastasiou et al .…”

“…Myocardial infarction was induced as previously reported (Karwi et al ., ). Briefly, rats were anaesthetized using thiobutabarbital (Inactin® 200 mg·kg −1 , i.p), and anaesthesia was maintained throughout the procedure by supplemental dosing (75 mg kg −1 , i.v.)…”

“…The roles of endogenous H 2 S, in a wide range of physiological systems, has been extensively explored following the discovery that it is produced by several regulated biochemical pathways in mammalian species (Kimura, ). In the myocardium, enhanced levels of H 2 S, whether by H 2 S supplement or increased endogenous production, have been shown to protect the heart against ischaemia/reperfusion injury (Johansen et al ., ; Elrod et al ., ; Karwi et al ., ). The exact cardioprotective mechanism of H 2 S has yet to be clarified, but a number of molecular targets have been identified.…”

Weight loss enhances cardiac energy metabolism and function in heart failure associated with obesity

“…Myocardial biopsies were collected at the end of perfusion for biochemical characterization, as previously described. [27][28][29] Briefly, protein samples (30 μg/well) were loaded onto 10% SDS-PAGE to be separated based on molecular weight, and were then transferred onto a nitrocellulose membrane using a wet-transfer method. The membrane was incubated with one of the following primary antibodies…”

Hexokinase 2 dimerization and interaction with voltage‐dependent anion channel promoted resistance to cell apoptosis induced by gemcitabine in pancreatic cancer

“…It was unknown whether ROS played important roles on HK2 dimerization. To determine the role of ROS, GYY4137, a reductant reducing the cellular ROS, was employed. When cells were pretreated with GYY4137, then treated by GEM, the HK2 dimer was reduced compared with only GEM treatment in SW1990 cells (Figure H).…”