Hydrogen sulfide protects against XXXX and reperfusion injury by activating AMP-activated protein kinase to  restore autophagic flux.

@entity296 @entity63 @entity1563 @entity28190 @entity1188 @entity741 @entity50461 @entity35 @entity28890
UNASSIGNED: How hydrogen sulfide (H2S) protects against @entity741 -reperfusion (I/R) injury is poorly understood. By using a slow-releasing H2S donor, we investigated if H2S protected against @entity296 /R injury by activating @entity28890 and restoring I/R-impaired autophagic flux. Male @entity35 received anterior descending @entity1563 followed by reperfusion. The H2S donor ADT and/or the @entity28890 inhibitor, compound C (CC), were administered after occlusion. @entity1188 was analyzed histologically. @entity28890 activation was assessed in the @entity63 heart by analyzing phosphorylation of @entity28890 and S6 ribosomal protein. Autophagy was assessed by analyzing the following markers: microtubule-associated protein 1 light chain 3 (LC3) I and II, @entity50461 ( @entity50461 ), @entity28190 and beclin-1. We further investigated if blocking autophagic flux with chloroquine abolished ADT cardioprotection in  vivo. Myocardial I/R reduced serum H2S levels, which was elevated by ADT. ADT enhanced @entity28890 activation and reduced @entity1188 following I/R, and both effects were abolished by @entity28890 inhibition. Myocardial I/R induced autophagosome accumulation, as evidenced by the increased ratios of LC3-II/LC3-I, upregulation of beclin-1 and @entity28190 and reduction in @entity50461 . ADT blunted these autophagic changes induced by I/R, indicating that ADT restored I/R-impaired autophagic flux. The @entity28890 inhibitor CC blocked ADT effects on restoring I/R-impaired autophagy flux. Moreover, chloroquine pretreatment abolished cardioprotection of ADT and increased autophagosome accumulation in the ADT-treated heart following I/R. In conclusion, @entity28890 activation and subsequent restoration of I/R-impaired autophagic flux are unrecognized mechanisms underlying cardioprotective effects conferred by H2S donors.
