title: 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/dt(max)) 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.
authors.affiliation: Department of Anesthesiology, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
authors.forename: Heng-Fei
authors.initials: HF
authors.lastname: Luan
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Zhao
authors.forename: Qi-Hong
authors.initials: QH
authors.lastname: Zhao
authors.forename: Pin
authors.initials: P
authors.lastname: Zhu
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Xiu
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis; D006862:Hydrogen Sulfide / Q000378:metabolism*; D057775:Ischemic Postconditioning; D053614:Janus Kinase 2 / Q000032:analysis / Q000378:metabolism*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D020032:Tyrphostins
chemical_list: D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D006862:Hydrogen Sulfide