Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway
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...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Associação Brasileira de Divulgação Científica
2012-10-01
|
Series: | Brazilian Journal of Medical and Biological Research |
Subjects: | |
Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012001000003&lng=en&tlng=en |
id |
doaj-09b02c2d45f04236a799a3de1c3a768e |
---|---|
record_format |
Article |
spelling |
doaj-09b02c2d45f04236a799a3de1c3a768e2020-11-24T22:43:30ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2012-10-01451089890510.1590/S0100-879X2012001000003S0100-879X2012001000003Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathwayHeng-Fei Luan0Zhi-Bin Zhao1Qi-Hong Zhao2Pin Zhu3Ming-Yu Xiu4Yong Ji5The First People’s Hospital of LianyungangThe First People’s Hospital of LianyungangThe First People’s Hospital of LianyungangThe First People’s Hospital of LianyungangThe First People’s Hospital of LianyungangThe First People’s Hospital of LianyungangThe 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012001000003&lng=en&tlng=enHydrogen sulfideJAK2/STAT3ApoptosisPostconditioningIschemia/reperfusion injury |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Heng-Fei Luan Zhi-Bin Zhao Qi-Hong Zhao Pin Zhu Ming-Yu Xiu Yong Ji |
spellingShingle |
Heng-Fei Luan Zhi-Bin Zhao Qi-Hong Zhao Pin Zhu Ming-Yu Xiu Yong Ji Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway Brazilian Journal of Medical and Biological Research Hydrogen sulfide JAK2/STAT3 Apoptosis Postconditioning Ischemia/reperfusion injury |
author_facet |
Heng-Fei Luan Zhi-Bin Zhao Qi-Hong Zhao Pin Zhu Ming-Yu Xiu Yong Ji |
author_sort |
Heng-Fei Luan |
title |
Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway |
title_short |
Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway |
title_full |
Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway |
title_fullStr |
Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway |
title_full_unstemmed |
Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway |
title_sort |
hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the jak2/stat3 survival pathway |
publisher |
Associação Brasileira de Divulgação Científica |
series |
Brazilian Journal of Medical and Biological Research |
issn |
1414-431X |
publishDate |
2012-10-01 |
description |
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. |
topic |
Hydrogen sulfide JAK2/STAT3 Apoptosis Postconditioning Ischemia/reperfusion injury |
url |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012001000003&lng=en&tlng=en |
work_keys_str_mv |
AT hengfeiluan hydrogensulfidepostconditioningprotectsisolatedratheartsagainstischemiaandreperfusioninjurymediatedbythejak2stat3survivalpathway AT zhibinzhao hydrogensulfidepostconditioningprotectsisolatedratheartsagainstischemiaandreperfusioninjurymediatedbythejak2stat3survivalpathway AT qihongzhao hydrogensulfidepostconditioningprotectsisolatedratheartsagainstischemiaandreperfusioninjurymediatedbythejak2stat3survivalpathway AT pinzhu hydrogensulfidepostconditioningprotectsisolatedratheartsagainstischemiaandreperfusioninjurymediatedbythejak2stat3survivalpathway AT mingyuxiu hydrogensulfidepostconditioningprotectsisolatedratheartsagainstischemiaandreperfusioninjurymediatedbythejak2stat3survivalpathway AT yongji hydrogensulfidepostconditioningprotectsisolatedratheartsagainstischemiaandreperfusioninjurymediatedbythejak2stat3survivalpathway |
_version_ |
1725695479307567104 |