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Inhibition of 12/15 lipoxygenase by baicalein reduces myocardial ischemia/reperfusion injury via modulation of multiple signaling pathways

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Abstract

12/15-Lipoxygenase (LOX) is a member of the LOX family that catalyzes the step from arachidonic acid to hydroxy-eicosatetraenoic acids (HETEs). Previous studies demonstrated that 12/15-LOX plays a critical role in the development of atherosclerosis, hypertension, heart failure, and other diseases; however, its role in myocardial ischemic injury was contraversal. Here, we investigated the inhibition of 12/15-LOX by baicalein on acute cardiac injury and dissected its molecular mechanism. In a mouse model of acute ischemia/reperfusion (I/R) injury, 12/15-LOX was significantly upregulated in the peri-infarct area surrounding the primary infarction. In cultured cardiac myocytes, baicalein suppressed apoptosis and caspase 3 activity in response to simulated ischemia/reperfusion (I/R). Moreover, administration of 12/15-LOX inhibitor, baicalein, significantly attenuated myocardial infarct size induced by I/R injury. Moreover, baicalein treatment significantly inhibited cardiomyocyte apoptosis, inflammatory responses and oxidative stress in the heart after I/R injury. The mechanisms underlying these effects were associated with the activation of ERK1/2 and AKT pathways and inhibition of activation of p38 MAPK, JNK1/2, and NF-kB/p65 pathways in the I/R-treated hearts and neonatal cardiomyoctes. Our data indicated that 12/15-LOX inhibitor baicalein can prevent myocardial I/R injury by modulation of multiple mechanisms, and suggest that baicalein could represent a novel therapeutic drug for acute myocardial infarction.

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Acknowledgments

This work was supported by China National Natural Science Funds (Nos. 81025001, 81330003 and 510025), Chang Jiang Scholar Program and the Beijing high-level talents program (PHR20110507).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Physiology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, Ministry of Education, No. 10 Xitoutiao You An Men, Beijing, 100069, China

    Lina Song, Hui Yang, Hong-Xia Wang, Cui Tian, Yu Liu, Xiang-Jun Zeng, Jie Du & Hui-Hua Li

  2. Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China

    Lina Song, Hui Yang, Hong-Xia Wang, Cui Tian, Yu Liu, Xiang-Jun Zeng, Jie Du & Hui-Hua Li

  3. Center for Translational Medicine, Temple University School of Medicine, Philadelphia, 19140, USA

    Erhe Gao

  4. Department of Physiology and Pathophysiology Xi’an Jiaotong University Cardiovascular Research Center, Xi’an Jiaotong University School of Medicine, Xi’an, 710061, China

    Yu-Ming Kang

Authors
  1. Lina Song
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  2. Hui Yang
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  10. Hui-Hua Li
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Correspondence to Hui-Hua Li.

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Song, L., Yang, H., Wang, HX. et al. Inhibition of 12/15 lipoxygenase by baicalein reduces myocardial ischemia/reperfusion injury via modulation of multiple signaling pathways. Apoptosis 19, 567–580 (2014). https://doi.org/10.1007/s10495-013-0946-z

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