title: Carbon monoxide releasing molecule‑2 attenuated ischemia/reperfusion‑induced apoptosis in cardiomyocytes via a mitochondrial pathway.
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.
authors: Department of Emergency, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors: Shen
authors: S
authors: Zhao
authors: Department of Emergency, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors: Qingming
authors: Q
authors: Lin
authors: Department of Emergency, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors: Heng
authors: H
authors: Li
authors: Department of Emergency, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors: Yumin
authors: Y
authors: He
authors: Department of Emergency, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors: Xiangshao
authors: X
authors: Fang
authors: Provincial Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
authors: Feng
authors: F
authors: Chen
authors: Taiping People's Hospital of Dongguan City, Dongguan, Guangdong 523900, P.R. China.
authors: Changwei
authors: C
authors: Chen
authors: Department of Emergency, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors: Zitong
authors: Z
authors: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002248:Carbon Monoxide / Q000378:metabolism*; D053148:Caspase 3 / Q000096:biosynthesis; D045304:Cytochromes c / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D009942:Organometallic Compounds / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C494774:Bak1 protein, rat; D009942:Organometallic Compounds; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D045304:Cytochromes c; D053148:Caspase 3