Journal Article

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

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

2014

Overview

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.

• Publisher: Springer New York,Springer Nature B.V
• Subject: Acute Disease / AKT protein / Animals / Apoptosis / Apoptosis - drug effects / Arachidonate 12-lipoxygenase / Arachidonate 12-Lipoxygenase - metabolism / Arachidonate 15-Lipoxygenase - metabolism / Arachidonic acid / Arteriosclerosis / Atherosclerosis / Biochemistry / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cardiomyocytes / Caspase-3 / Cell Biology / Cells, Cultured / Congestive heart failure / Extracellular signal-regulated kinase / Flavanones - pharmacology / Flavanones - therapeutic use / Heart diseases / Hypertension / Inflammation - metabolism / Inhibitors / Injury prevention / Ischemia / Lipoxygenase / Lipoxygenase Inhibitors - pharmacology / Lipoxygenase Inhibitors - therapeutic use / Liquid oxygen / MAP kinase / Mice / Mice, Inbred C57BL / Modulation / Molecular modelling / Myocardial infarction / Myocardial Infarction - metabolism / Myocardial Infarction - pathology / Myocardial Infarction - prevention & control / Myocardial ischemia / Myocardial Reperfusion Injury - metabolism / Myocardial Reperfusion Injury - pathology / Myocardial Reperfusion Injury - prevention & control / Myocardium - metabolism / Myocardium - pathology / Myocytes / Myocytes, Cardiac - drug effects / Myocytes, Cardiac - metabolism / Myocytes, Cardiac - pathology / Neonates / NF-κB protein / Oncology / Original Paper / Oxidative stress / Oxidative Stress - drug effects / Rats / Reperfusion / Signal Transduction / Virology