N-n-butyl haloperidol iodide ameliorates hypoxia/reoxygenation injury through modulating the LKB1/AMPK/ROS pathway in cardiac microvascular endothelial cells.
Endothelial cells are highly sensitive to hypoxia and contribute to myocardial ischemia/reperfusion injury. We have reported that N-n-butyl haloperidol iodide (F2) can attenuate hypoxia/reoxygenation (H/R) injury in cardiac microvascular endothelial cells (CMECs). However, the molecular mechanisms remain unclear. Neonatal rat CMECs were isolated and subjected to H/R. Pretreatment of F2 leads to a reduction in H/R injury, as evidenced by increased cell viability, decreased lactate dehydrogenase (LDH) leakage and apoptosis, together with enhanced AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1) phosphorylation in H/R ECs. Blockade of AMPK with compound C reversed F2-induced inhibition of H/R injury, as evidenced by decreased cell viability, increased LDH release and apoptosis. Moreover, compound C also blocked the ability of F2 to reduce H/R-induced reactive oxygen species (ROS) generation. Supplementation with the ROS scavenger N-acetyl-L-cysteine (NAC) reduced ROS levels, increased cell survival rate, and decreased both LDH release and apoptosis after H/R. In conclusion, our data indicate that F2 may mitigate H/R injury by stimulating LKB1/AMPK signaling pathway and subsequent suppression of ROS production in CMECs.
['Lu|Binger|B|', 'Wang|Bin|B|', 'Zhong|Shuping|S|', 'Zhang|Yanmei|Y|', 'Gao|Fenfei|F|', 'Chen|Yicun|Y|', 'Zheng|Fuchun|F|', 'Shi|Ganggang|G|']
D000091162:AMP-Activated Protein Kinase Kinases D055372:AMP-Activated Protein Kinases D000111:Acetylcysteine D000818:Animals D017209:Apoptosis D015687:Cell Hypoxia D002470:Cell Survival D042783:Endothelial Cells D006220:Haloperidol D007511:Ischemia D007770:L-Lactate Dehydrogenase D010766:Phosphorylation D017346:Protein Serine-Threonine Kinases D051381:Rats D017207:Rats, Sprague-Dawley D017382:Reactive Oxygen Species
N-n-butyl haloperidol iodide hypoxia/reoxygenation LKB1/AMPK/ROS cardiac microvascular endothelial cells