https://scholars.lib.ntu.edu.tw/handle/123456789/616148
標題: | Baicalein Preconditioning Cardioprotection Involves Pro-Oxidant Signaling and Activation of Pyruvate Dehydrogenase | 作者: | Li, Jing WEI-TIEN CHANG Qin, Gina Wojcik, Kimberly R Li, Chang-Qing Hsu, Chin-Wang Han, Mei Zhu, Xiangdong Vanden Hoek, Terry L Shao, Zuo-Hui |
關鍵字: | Akt; Baicalein Preconditioning; Ischemia/Reperfusion; Mitochondrial Complex III; Pro-Oxidant; Pyruvate Dehydrogenase; ROS | 公開日期: | 23-六月-2022 | 來源出版物: | The American journal of Chinese medicine | 摘要: | Preconditioning has a powerful protective potential against myocardial ischemia-reperfusion injury (I/R). Our prior work demonstrated that baicalein, a flavonoid derived from the root of Scatellaria baicalensis Georgi (also known as Huangqin), confers this preconditioning protection. This study further explored the mechanisms of baicalein preconditioning (BC-PC) in mouse cardiomyocytes. Cells were treated with baicalein (10 [Formula: see text] M) for a brief period of time (10 min) prior to simulated ischemia 90 min/reperfusion for 180 min. Baicalein triggered an induction of a small amount of mitochondrial reactive oxygen species (ROS) prior to the initiation of ischemia, assessed by 6-carboxy-2', 7'-dichlorodihydrofluorescein diacetate (6-carboxy-H2DCFDA). It also significantly increased cell viability measured by propidium iodide (PI) and lactate dehydrogenase and preserved mitochondrial membrane potential assessed by TMRM fluorescence intensity. Myxothiazol, a mitochondrial electron transport chain complex III inhibitor, partially blocked ROS generation induced by BC-PC and reduced cell viability. BC-PC increased phosphorylation of Akt (Thr308 and Ser473) and eNOS Ser1177, and nitric oxide (NO) production measured using 4,5-diaminofluorescein diacetate (DAF-2 DA, 1 [Formula: see text] M). Akt inhibitor API-2 abolished Akt phosphorylation and reduced DAF-2 production and cell viability. In addition, BC-PC decreased phosphorylation of pyruvate dehydrogenase (PDH) reflecting upregulated PDH activity, and increased ATP production at 30 min during reperfusion. Taken together, baicalein preconditioning-induced cardioprotection involves pro-oxidant generation, activates survival signaling Akt/eNOS/NO, and improves metabolic recovery after I/R injury. Our work provides new perspectives on the effect of baicalein on cardiac preconditioning against I/R injury. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/616148 | ISSN: | 0192415X | DOI: | 10.1142/S0192415X22500513 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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