Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway

Abstract

The JAK2/STAT3 signal pathway is an important component of survivor activating factor enhancement (SAFE) pathway. The objective of the present study was to determine whether the JAK2/STAT3 signaling pathway participates in hydrogen sulfide (H2S) postconditioning, protecting isolated rat hearts from ischemic-reperfusion injury. Male Sprague-Dawley rats (230-270 g) were divided into 6 groups (N = 14 per group): time-matched perfusion (Sham) group, ischemia/reperfusion (I/R) group, NaHS postconditioning group, NaHS with AG-490 group, AG-490 (5 µM) group, and dimethyl sulfoxide (DMSO; <0.2%) group. Langendorff-perfused rat hearts, with the exception of the Sham group, were subjected to 30 min of ischemia followed by 90 min of reperfusion after 20 min of equilibrium. Heart rate, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of increase or decrease of left ventricular pressure (± dp/dtmax) were recorded. Infarct size was determined using triphenyltetrazolium chloride (TTC) staining. Myocardial TUNEL staining was used as the in situ cell death detection method and the percentage of TUNEL-positive nuclei to all nuclei counted was used as the apoptotic index. The expression of STAT3, bcl-2 and bax was determined by Western blotting. After reperfusion, compared to the I/R group, H2S significantly improved functional recovery and decreased infarct size (23.3 ± 3.8 vs 41.2 ± 4.7%, P < 0.05) and apoptotic index (22.1 ± 3.6 vs 43.0 ± 4.8%, P < 0.05). However, H2S-mediated protection was abolished by AG-490, the JAK2 inhibitor. In conclusion, H2S postconditioning effectively protects isolated I/R rat hearts via activation of the JAK2/STAT3 signaling pathway.

Honokiol protects against renal ischemia/reperfusion injury via the suppression of oxidative stress, iNOS, inflammation and STAT3 in rats

“…Yu et al suggested that honokiol exerts pro-apoptotic effects on transformed Barrett's cells through inhibition of STAT3 (42). Luan et al reported that honokiol induces cell cycle arrest and apoptosis through inhibiting the DNA binding of nuclear factor-κB and STAT3 (43). In the present study, honokiol administration significantly decreased the levels of caspase-3 in the IRI rats.…”

The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning

“…Bian et al (2006) showed that blockade of mitoKATP channels with 5-hydroxydecanoic acid had no effect on the cardioprotection afforded by exogenous H2S, suggesting that contrary to the mechanism of classic PC, mitoKATP channels most probably do not play a major role in the cardioprotection afforded by H2S. However, other studies (Johansen et al, 2006;Rossoni et al, 2008) have shown that pre-treatment with the KATP channel blockers glibenclamide or 5-hydroxydecanoate abolished the infarct-limiting effect of NaHS.Concerning the effect of H2S on PostC, studies in isolated hearts have shown that treatment with NaHS at the onset of reperfusion results in a reduction of infarct size (Luan et al, 2012), a cardioprotective effect similar to that of PostC (Ji et al, 2008). In another study, treatment with NaHS also resulted in a significant improvement in LV function and reduction of arrhythmia scores .…”

Exogenous hydrogen sulfide promotes hepatocellular carcinoma cell growth by activating the STAT3-COX-2 signaling pathway

“…However, the potential mechanism of H 2 S in cancer is unclear and controversial. Accumulating evidences have demonstrated that H 2 S promotes cancer progression, including proliferation, migration and invasion (28)(29)(30)(31)(32)(33)(34). H 2 S can protect cancer cells from chemopreventive agent β-phenylethyl isothiocyanate-induced apoptosis (30) and promote proliferation (30), which may be mediated by the increase in Akt and extracellular signal-regulated kinase (ERK) phosphorylation, and the decrease in p21 Waf1/Cip1 expression and NO production.…”

“…Those results indicate that H 2 S promotes cancer cell growth. Notably, H 2 S post-conditioning effectively protects isolated ischemia/reperfusion rat hearts via activation of the Janus kinase 2 (JAK2)/STAT3 signaling pathway (33). However, whether the STAT3-COX-2 signaling pathway contributes to the growth effect of exogenous H 2 S on HCC cells remains unclear.…”