Apoptosis

, Volume 19, Issue 4, pp 567–580

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

  • Lina Song
  • Hui Yang
  • Hong-Xia Wang
  • Cui Tian
  • Yu Liu
  • Xiang-Jun Zeng
  • Erhe Gao
  • Yu-Ming Kang
  • Jie Du
  • Hui-Hua Li
Original Paper

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.

Keywords

Baicalein 12/15-Lipoxygenase Ischemia/reperfusion Cardiac injury Signaling pathway 

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Lina Song
    • 1
    • 2
  • Hui Yang
    • 1
    • 2
  • Hong-Xia Wang
    • 1
    • 2
  • Cui Tian
    • 1
    • 2
  • Yu Liu
    • 1
    • 2
  • Xiang-Jun Zeng
    • 1
    • 2
  • Erhe Gao
    • 3
  • Yu-Ming Kang
    • 4
  • Jie Du
    • 1
    • 2
  • Hui-Hua Li
    • 1
    • 2
  1. 1.Department of Pathology, Physiology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical SciencesCapital Medical University, Ministry of EducationBeijingChina
  2. 2.Beijing Institute of Heart, Lung and Blood Vessel DiseasesBeijingChina
  3. 3.Center for Translational MedicineTemple University School of MedicinePhiladelphiaUSA
  4. 4.Department of Physiology and Pathophysiology Xi’an Jiaotong University Cardiovascular Research CenterXi’an Jiaotong University School of MedicineXi’anChina

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