Concentration-dependent Wrestling between Detrimental and Protective Effects of H2O2 during Myocardial Ischemia/Reperfusion
Jul 01, 2014 Email"> PrintText Size
Reperfusion injury after acute myocardial ischemia is a complex phenomenon that consists of mechanical dysfunction and cell death. Reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress are paradoxically implicated in myocardial ischemia/reperfusion (I/R) injury and cardioprotection. However, the precise interpretation for the dual role of ROS and its relationship with the ER stress during I/R remain elusive.
To solve these issues, a team of researchers, led by Dr. YANG Huangtian, at the Institute of Health Science, investigated the concentration-dependent effects of hydrogen peroxide (H2O2) preconditioning (PC) and postconditioning (PoC) on the ER stress and pro-survival reperfusion injury salvage kinases (RISK) activation using an ex vivo rat myocardial I/R model.
They showed three phases in the effects of H2O2PC and PoC in myocardial I/R injury and protection. H2O2PC and PoC at the moderate level (10-300 mmol/L) concentration-dependently improved the post-ischemic recovery of cardiac performance though the activation of RISK pathway. In contrast, H2O2 exacerbated I/R-induced contractile dysfunction via the enhancement of I/R-induced ER stress at the low level (1 mM), and promoted the oxidative stress at the high level (≧100 mmol/L).
These findings demonstrate that the differential effects of H2O2 are derived from a quantity-dependent wrestling between its detrimental and signaling roles. This study provides a new angle to interpret the controversial roles of ROS in myocardial I/R and suggests a hint for cardiologists to reconsider the clinical translation of cardioprotective strategies.
This study entitled “Concentration-dependent wrestling between detrimental and protective effects of H2O2 during myocardial ischemia/reperfusion” was published online in Cell Death and Disease on Jun 19, 2014, and was supported by the Major State Basic Research Development Program of China, National Natural Sciences Foundation of China, and National Science and Technology Major Project of China.
(Image by Dr. YANG Huangtian‘s group)
Contact:
YANG Huangtian
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine,
Shanghai 200031, China
E-mail: htyang@sibs.ac.cn
Reperfusion injury after acute myocardial ischemia is a complex phenomenon that consists of mechanical dysfunction and cell death. Reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress are paradoxically implicated in myocardial ischemia/reperfusion (I/R) injury and cardioprotection. However, the precise interpretation for the dual role of ROS and its relationship with the ER stress during I/R remain elusive.
To solve these issues, a team of researchers, led by Dr. YANG Huangtian, at the Institute of Health Science, investigated the concentration-dependent effects of hydrogen peroxide (H2O2) preconditioning (PC) and postconditioning (PoC) on the ER stress and pro-survival reperfusion injury salvage kinases (RISK) activation using an ex vivo rat myocardial I/R model.
They showed three phases in the effects of H2O2PC and PoC in myocardial I/R injury and protection. H2O2PC and PoC at the moderate level (10-300 mmol/L) concentration-dependently improved the post-ischemic recovery of cardiac performance though the activation of RISK pathway. In contrast, H2O2 exacerbated I/R-induced contractile dysfunction via the enhancement of I/R-induced ER stress at the low level (1 mM), and promoted the oxidative stress at the high level (≧100 mmol/L).
These findings demonstrate that the differential effects of H2O2 are derived from a quantity-dependent wrestling between its detrimental and signaling roles. This study provides a new angle to interpret the controversial roles of ROS in myocardial I/R and suggests a hint for cardiologists to reconsider the clinical translation of cardioprotective strategies.
(Image by Dr. YANG Huangtian‘s group)
Contact:
YANG Huangtian
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine,
Shanghai 200031, China
E-mail: htyang@sibs.ac.cn
CAS Institutes
There are 124 Institutions directly under the CAS by the end of 2012, with 104 research institutes, five universities & supporting organizations, 12 management organizations that consist of the headquarters and branches, and three other units. Moreover, there are 25 legal entities affiliated and 22 CAS invested holding enterprisesThere are 124 I...>> more
Contact Us
Chinese Academy of Sciences
Add: 52 Sanlihe Rd., Xicheng District, Beijing, China
Postcode: 100864
Tel: 86-10-68597592 (day) 86-10-68597289 (night)
Fax: 86-10-68511095 (day) 86-10-68512458 (night)
E-mail: cas_en@cas.cn