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Int. J. Mol. Sci. 2018, 19(4), 973; https://doi.org/10.3390/ijms19040973

Baicalein Rescues Delayed Cooling via Preservation of Akt Activation and Akt-Mediated Phospholamban Phosphorylation

1
Center of Advanced Resuscitation Medicine, Center for Cardiovascular Research, Department of Emergency Medicine, University of Illinois Hospital, and Health Sciences System, Chicago, IL 60612, USA
2
Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
3
Department of Emergency Medicine, Taipei Veterans General Hospital and Emergency Medicine, College of Medicine, National Yang-Ming University, Taipei 112, Taiwan
4
Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL 60637, USA
*
Authors to whom correspondence should be addressed.
Received: 15 February 2018 / Revised: 20 March 2018 / Accepted: 22 March 2018 / Published: 24 March 2018
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2018)
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Abstract

Cooling reduces the ischemia/reperfusion (I/R) injury seen in sudden cardiac arrest (SCA) by decreasing the burst of reactive oxygen species (ROS). Its cardioprotection is diminished when delay in reaching the target temperature occurs. Baicalein, a flavonoid derived from the root of Scutellaria baicalensis Georgi, possesses antioxidant properties. Therefore, we hypothesized that baicalein can rescue cooling cardioprotection when cooling is delayed. Two murine cardiomyocyte models, an I/R model (90 min ischemia/3 h reperfusion) and stunning model (30 min ischemia/90 min reperfusion), were used to assess cell survival and contractility, respectively. Cooling (32 °C) was initiated either during ischemia or during reperfusion. Cell viability and ROS generation were measured. Cell contractility was evaluated by real-time phase-contrast imaging. Our results showed that cooling reduced cell death and ROS generation, and this effect was diminished when cooling was delayed. Baicalein (25 µM), given either at the start of reperfusion or start of cooling, resulted in a comparable reduction of cell death and ROS production. Baicalein improved phospholamban phosphorylation, contractility recovery, and cell survival. These effects were Akt-dependent. In addition, no synergistic effect was observed with the combined treatments of cooling and baicalein. Our data suggest that baicalein may serve as a novel adjunct therapeutic strategy for SCA resuscitation. View Full-Text
Keywords: intraischemic cooling; delayed cooling; baicalein; ischemia/reperfusion; reactive oxygen species (ROS); cardiomyocyte; Akt; cell death; contractility intraischemic cooling; delayed cooling; baicalein; ischemia/reperfusion; reactive oxygen species (ROS); cardiomyocyte; Akt; cell death; contractility
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Shao, Z.; Chen, S.-J.; Zhu, X.; Lee, C.; Huang, H.-H.; Meliton, A.; Li, C.; Hoek, T.L.V.; Li, J. Baicalein Rescues Delayed Cooling via Preservation of Akt Activation and Akt-Mediated Phospholamban Phosphorylation. Int. J. Mol. Sci. 2018, 19, 973.

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