Baicalein preconditioning protects cardiomyocytes from ischemia-reperfusion injury via mitochondrial oxidant signaling

Wei Tien Chang, Jing Li, Matthew S. Vanden Hoek, Xiangdong Zhu, Chang Qing Li, Hsien Hao Huang, Chin Wang Hsu, Qiang Zhong, Juan Li, Sy Jou Chen, Terry L. Vanden Hoek, Zuo Hui Shao

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Abstract

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.

Original languageEnglish
Pages (from-to)315-331
Number of pages17
JournalAmerican Journal of Chinese Medicine
Volume41
Issue number2
DOIs
Publication statusPublished - 2013

Fingerprint

Reperfusion Injury
Cardiac Myocytes
Oxidants
Reperfusion
Ischemia
DNA Fragmentation
Anions
Reactive Oxygen Species
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Stilbenes
Propidium
Electron Transport Complex III
Acetylcysteine
baicalein
Cell Survival
Cell Death
Antioxidants
Fluorescence
Apoptosis
Acids

Keywords

  • Anion Channel
  • ATP-Dependent Potassium Channel
  • Baicalein
  • Mitochondria
  • Oxidant
  • Preconditioning
  • Reperfusion

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Baicalein preconditioning protects cardiomyocytes from ischemia-reperfusion injury via mitochondrial oxidant signaling. / Chang, Wei Tien; Li, Jing; Vanden Hoek, Matthew S.; Zhu, Xiangdong; Li, Chang Qing; Huang, Hsien Hao; Hsu, Chin Wang; Zhong, Qiang; Li, Juan; Chen, Sy Jou; Vanden Hoek, Terry L.; Shao, Zuo Hui.

In: American Journal of Chinese Medicine, Vol. 41, No. 2, 2013, p. 315-331.

Research output: Contribution to journalArticle

Chang, WT, Li, J, Vanden Hoek, MS, Zhu, X, Li, CQ, Huang, HH, Hsu, CW, Zhong, Q, Li, J, Chen, SJ, Vanden Hoek, TL & Shao, ZH 2013, 'Baicalein preconditioning protects cardiomyocytes from ischemia-reperfusion injury via mitochondrial oxidant signaling', American Journal of Chinese Medicine, vol. 41, no. 2, pp. 315-331. https://doi.org/10.1142/S0192415X13500237
Chang, Wei Tien ; Li, Jing ; Vanden Hoek, Matthew S. ; Zhu, Xiangdong ; Li, Chang Qing ; Huang, Hsien Hao ; Hsu, Chin Wang ; Zhong, Qiang ; Li, Juan ; Chen, Sy Jou ; Vanden Hoek, Terry L. ; Shao, Zuo Hui. / Baicalein preconditioning protects cardiomyocytes from ischemia-reperfusion injury via mitochondrial oxidant signaling. In: American Journal of Chinese Medicine. 2013 ; Vol. 41, No. 2. pp. 315-331.
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AU - Li, Chang Qing

AU - Huang, Hsien Hao

AU - Hsu, Chin Wang

AU - Zhong, Qiang

AU - Li, Juan

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AU - Vanden Hoek, Terry L.

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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.

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KW - Reperfusion

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