Carbon monoxide releasing molecule‑2 attenuated ischemia/reperfusion‑induced apoptosis in cardiomyocytes via a mitochondrial pathway

Zhao,Shen; Lin,Qingming; Li,Heng; He,Yumin; Fang,Xiangshao; Chen,Feng; Chen,Changwei; Huang,Zitong

doi:10.3892/mmr.2013.1861

Carbon monoxide releasing molecule‑2 attenuated ischemia/reperfusion‑induced apoptosis in cardiomyocytes via a mitochondrial pathway

Authors:
- Shen Zhao
- Qingming Lin
- Heng Li
- Yumin He
- Xiangshao Fang
- Feng Chen
- Changwei Chen
- Zitong Huang
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Affiliations: Department of Emergency, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China, Provincial Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China, Taiping People's Hospital of Dongguan City, Dongguan, Guangdong 523900, P.R. China
Published online on: December 13, 2013 https://doi.org/10.3892/mmr.2013.1861
Pages: 754-762

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Abstract

Carbon monoxide (CO) is an endogenous gaseous transmitter that exerts multi‑protection in ischemia/reperfusion (I/R) injury, but few experimental studies regarding CO on myocardial I/R‑induced apoptosis, as well as its underlying mechanism have been conducted. The present study was designed to investigate whether CO released from CO‑releasing molecule‑2 (CORM‑2) is capable of ameliorating myocardial I/R‑induced apoptosis via a mitochondrial apoptotic pathway. Primary cultures of neonatal rat cardiomyocytes were randomly distributed into four groups: Control, I/R (cultured cardiomyocytes were subjected to 2 h simulated ischemia followed by 4 h reperfusion), CORM‑2 and inactive CORM‑2 (iCORM‑2) groups (20 µM CORM‑2 and 20 µM iCORM‑2 were administered at the beginning of reperfusion following ischemia, respectively). Flow cytometric analysis showed that CORM‑2 treatment significantly decreased apoptosis of cardiomyocytes triggered by simulated I/R. CORM‑2 partially recovered mitochondrial respiration and ultrastructure alteration, and lowered caspase‑3 expression and the release of cytochrome c. Furthermore, CORM‑2 partly reduced BAK/BAX expression in mitochondria, as well as the BAX level in the cytoplasm. Cardioprotection is lost when CORM‑2 is replaced by iCORM‑2. CORM‑2 treatment, at the time of reperfusion, was concluded to attenuate myocardial I/R‑induced apoptosis. The protection mechanisms may be targeted to the mitochondria and involved in the inhibition of the BAK/BAX‑mediated intrinsic pathway.

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