TY - JOUR
T1 - Baicalein preconditioning protects cardiomyocytes from ischemia-reperfusion injury via mitochondrial oxidant signaling
AU - Chang, Wei Tien
AU - Li, Jing
AU - Vanden Hoek, Matthew S.
AU - Zhu, Xiangdong
AU - Li, Chang Qing
AU - Huang, Hsien Hao
AU - Hsu, Chin Wang
AU - Zhong, Qiang
AU - Li, Juan
AU - Chen, Sy Jou
AU - Vanden Hoek, Terry L.
AU - Shao, Zuo Hui
N1 - Funding Information:
This study was supported by grants NIH/NCCAM AT01575, AT003441.
PY - 2013
Y1 - 2013
N2 - Previous studies suggest baicalein, in addition to its antioxidant effects, protects against hypoxia/reoxygenation injury via its pro-oxidant properties. We hypothesize that a brief period of baicalein treatment prior to ischemia/reperfusion (I/R) may trigger preconditioning protection via a mitochondrial pro-oxidant mechanism. Using an established chick cardiomyocyte model of I/R, cells were preconditioned with baicalein (10 μM) for 10 min followed by 10-min wash prior to I/R. Intracellular oxidants were measured using 2′, 7′-dichlorofluorescin diacetate (DCFH/DA). Cell viability was assessed by propidium iodide and apoptosis determined by DNA fragmentation. Baicalein induced a transient but significant increase of DCF fluorescence within the 10-min preconditioning period, and led to significant reduction of cell death (38.9 ± 1.8% vs. 58.7 ± 1.2% in I/R control, n = 6, p < 0.001) and DNA fragmentation after I/R. Cotreatment with N-acetylcysteine (500 μM), mitochondrial complex III electron transport chain inhibitor myxothiazol (1 μM), mitochondrial KATP channel blocker 5-hydroxydecanoate-Na (5-HD, 500 μM) or anion channel inhibitor 4′, 4′-diisothiocyanato-stilbene-2, 2′-disulfonic acid (DIDS, 200 μM) resulted in significant abrogation of oxidant increase during induction as well as the protection conferred by baicalein preconditioning. These results suggest that baicalein preconditioning exhibits significant anti-apoptotic protection against cardiomyocyte I/R injury by mitochondrial oxidant signaling, which was in part mediated by mitochondrial KATP channel and anion channel opening.
AB - Previous studies suggest baicalein, in addition to its antioxidant effects, protects against hypoxia/reoxygenation injury via its pro-oxidant properties. We hypothesize that a brief period of baicalein treatment prior to ischemia/reperfusion (I/R) may trigger preconditioning protection via a mitochondrial pro-oxidant mechanism. Using an established chick cardiomyocyte model of I/R, cells were preconditioned with baicalein (10 μM) for 10 min followed by 10-min wash prior to I/R. Intracellular oxidants were measured using 2′, 7′-dichlorofluorescin diacetate (DCFH/DA). Cell viability was assessed by propidium iodide and apoptosis determined by DNA fragmentation. Baicalein induced a transient but significant increase of DCF fluorescence within the 10-min preconditioning period, and led to significant reduction of cell death (38.9 ± 1.8% vs. 58.7 ± 1.2% in I/R control, n = 6, p < 0.001) and DNA fragmentation after I/R. Cotreatment with N-acetylcysteine (500 μM), mitochondrial complex III electron transport chain inhibitor myxothiazol (1 μM), mitochondrial KATP channel blocker 5-hydroxydecanoate-Na (5-HD, 500 μM) or anion channel inhibitor 4′, 4′-diisothiocyanato-stilbene-2, 2′-disulfonic acid (DIDS, 200 μM) resulted in significant abrogation of oxidant increase during induction as well as the protection conferred by baicalein preconditioning. These results suggest that baicalein preconditioning exhibits significant anti-apoptotic protection against cardiomyocyte I/R injury by mitochondrial oxidant signaling, which was in part mediated by mitochondrial KATP channel and anion channel opening.
KW - ATP-Dependent Potassium Channel
KW - Anion Channel
KW - Baicalein
KW - Mitochondria
KW - Oxidant
KW - Preconditioning
KW - Reperfusion
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U2 - 10.1142/S0192415X13500237
DO - 10.1142/S0192415X13500237
M3 - Article
C2 - 23548122
AN - SCOPUS:84876212549
SN - 0192-415X
VL - 41
SP - 315
EP - 331
JO - American Journal of Chinese Medicine
JF - American Journal of Chinese Medicine
IS - 2
ER -