Parthenolide-Induced Cytotoxicity in H9c2 Cardiomyoblasts Involves Oxidative Stress.
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.


BACKGROUND
Cardiomyoblast; Endoplasmic reticulum stress; Oxidative stress; Parthenolide; Reperfusion injury.
Cardiovascular Division, Lotung Poh-Ai Hospital, Luodong; ; Department of Biomedical Engineering, Chung Yuan Christian University, Chungli;
Tien-Yao
TY
Tsai
Division of Cardiology, Department of Medicine, Taipei Medical University Wan Fan Hospital, Taipei;
Paul
P
Chan
Department of Physiology, China Medical University;
Chi-Li
CL
Gong
Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan;
Kar-Lok
KL
Wong
Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan;
Tzu-Hui
TH
Su
Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai, China;
Pei-Chen
PC
Shen
Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan;
Yuk-Man
YM
Leung
Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University, Shanghai, China.
Zhong-Min
ZM
Liu