Tien-Yao Tsai1, Paul Chan2, Chi-Li Gong3, Kar-Lok Wong4, Tzu-Hui Su4, Pei-Chen Shen5, Yuk-Man Leung6, Zhong-Min Liu7. 1. Cardiovascular Division, Lotung Poh-Ai Hospital, Luodong; ; Department of Biomedical Engineering, Chung Yuan Christian University, Chungli; 2. Division of Cardiology, Department of Medicine, Taipei Medical University Wan Fan Hospital, Taipei; 3. Department of Physiology, China Medical University; 4. Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan; 5. Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai, China; 6. Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan; 7. Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University, Shanghai, China.
Abstract
BACKGROUND: Cardiac cellular injury as a consequence of ischemia and reperfusion involves nuclear factor-κB (NF-κ B), amongst other factors, and NF-κ B inhibitors could substantially reduce myocardial infarct size. Parthenolide, a sesquiterpene lactone compound which could inhibit NF-κ B, has been shown to ameliorate myocardial reperfusion injury but may also produce toxic effects in cardiomyocytes at high concentrations. The aim of this study was to examine the cytotoxic effects of this drug on H9c2 cardiomyoblasts, which are precursor cells of cardiomyocytes. METHODS: Cell viability and apoptosis were examined by MTT and TUNEL assay, respectively, and protein expression was analyzed by western blot. Reactive oxygen species (ROS) production was measured using DCFH-DA as dye. Cytosolic Ca(2+) concentration and mitochondrial membrane potential were measured microfluorimetrically using, respectively, fura 2 and rhodamine 123 as dyes. RESULTS: Parthenolide caused apoptosis at 30 μ M, as judged by TUNEL assay and Bax and cytochrome c translocation. It also caused collapse of mitochondrial membrane potential and endoplasmic reticulum stress. Parthenolide triggered ROS formation, and vitamin C (antioxidant) partially alleviated parthenolide-induced cell death. CONCLUSIONS: The results suggested that parthenolide at high concentrations caused cytotoxicity in cardiomyoblasts in part by inducing oxidative stress, and demonstrated the imperative for cautious and appropriate use of this agent in cardioprotection. KEY WORDS: Cardiomyoblast; Endoplasmic reticulum stress; Oxidative stress; Parthenolide; Reperfusion injury.
BACKGROUND:Cardiac cellular injury as a consequence of ischemia and reperfusion involves nuclear factor-κB (NF-κ B), amongst other factors, and NF-κ B inhibitors could substantially reduce myocardial infarct size. Parthenolide, a sesquiterpene lactone compound which could inhibit NF-κ B, has been shown to ameliorate myocardial reperfusion injury but may also produce toxic effects in cardiomyocytes at high concentrations. The aim of this study was to examine the cytotoxic effects of this drug on H9c2 cardiomyoblasts, which are precursor cells of cardiomyocytes. METHODS: Cell viability and apoptosis were examined by MTT and TUNEL assay, respectively, and protein expression was analyzed by western blot. Reactive oxygen species (ROS) production was measured using DCFH-DA as dye. Cytosolic Ca(2+) concentration and mitochondrial membrane potential were measured microfluorimetrically using, respectively, fura 2 and rhodamine 123 as dyes. RESULTS:Parthenolide caused apoptosis at 30 μ M, as judged by TUNEL assay and Bax and cytochrome c translocation. It also caused collapse of mitochondrial membrane potential and endoplasmic reticulum stress. Parthenolide triggered ROS formation, and vitamin C (antioxidant) partially alleviated parthenolide-induced cell death. CONCLUSIONS: The results suggested that parthenolide at high concentrations caused cytotoxicity in cardiomyoblasts in part by inducing oxidative stress, and demonstrated the imperative for cautious and appropriate use of this agent in cardioprotection. KEY WORDS: Cardiomyoblast; Endoplasmic reticulum stress; Oxidative stress; Parthenolide; Reperfusion injury.
Authors: Réka Skoumal; Miklós Tóth; Raisa Serpi; Jaana Rysä; Hanna Leskinen; Johanna Ulvila; Tarja Saiho; Jani Aro; Heikki Ruskoaho; István Szokodi; Risto Kerkelä Journal: J Mol Cell Cardiol Date: 2011-01-09 Impact factor: 5.000