20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells
20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells
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DOI：
10.1152/ajpheart.01087.2008
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发表时间：
2009-03-01
影响因子：
4.8
通讯作者：
Jacobs, Elizabeth R.
中科院分区：
文献类型：
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作者：
Dhanasekaran, Anuradha;Bodiga, Sreedhar;Jacobs, Elizabeth R.
Dhanasekaran A，Bodiga S，Gruenloh S，Gao Y，Dunn L，法尔克JR，Buonaccorsi JN，Medhora M，Jacobs ER. 20-HETE增加肺动脉和肺动脉内皮细胞的存活率并减少凋亡。Am J Physiol Heart Circ Physiol 296：H777-H786，2009。首次发表于2009年1月9日; doi：10.1152/ajpheart.01087.2008。20-羟基二十碳四烯酸（20-HETE）是一种存在于血管平滑肌中的内源性细胞色素P-450产物，并且独特地位于肺动脉（PA）的血管内皮中。20-HETE以NADPH氧化酶依赖性方式增强牛PA内皮细胞（BPAEC）的活性氧（ROS）产生，并被认为通过激活全身血管床中的该途径促进血管生成。我们测试了20-HETE或该化合物的稳定类似物20-羟基-二十碳-5（Z），14（Z）-二烯酸在血清饥饿应激的BPAEC中增强存活和防止凋亡的能力。20-HETE使饥饿的BPAEC数量呈浓度依赖性增加，并增加5-溴-2 '-脱氧尿苷掺入。Caspase-3活性、核碎裂研究和3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物测定支持用20-HETE单次应用处理的饥饿BPAEC免于凋亡和增强存活。保护细胞凋亡依赖于完整的NADPH氧化酶，磷脂酰肌醇3（PI 3）-激酶，和ROS的生产。通过抑制PI 3激酶或Akt活性来阻断20-HETE刺激的BPAECs的ROS产生。这些数据表明，20-HETE相关的BPAEC细胞凋亡保护需要PI 3-激酶和Akt的激活和ROS的产生。20-HETE还保护脂多糖应激的BPAECs和暴露于缺氧/复氧离体的小鼠PA中的细胞凋亡。总之，20-HETE可能通过激活促生存PI 3-激酶和Akt途径、NADPH氧化酶激活和NADPH氧化酶衍生的超氧化物而为BPAEC提供存活优势。
Dhanasekaran A, Bodiga S, Gruenloh S, Gao Y, Dunn L, Falck JR, Buonaccorsi JN, Medhora M, Jacobs ER. 20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells. Am J Physiol Heart Circ Physiol 296: H777-H786, 2009. First published January 9, 2009; doi:10.1152/ajpheart.01087.2008.-20-Hydroxyeicosatetraenoic acid (20-HETE) is an endogenous cytochrome P-450 product present in vascular smooth muscle and uniquely located in the vascular endothelium of pulmonary arteries (PAs). 20-HETE enhances reactive oxygen species (ROS) production of bovine PA endothelial cells (BPAECs) in an NADPH oxidase-dependent manner and is postulated to promote angiogenesis via activation of this pathway in systemic vascular beds. We tested the capacity of 20-HETE or a stable analog of this compound, 20-hydroxy-eicosa-5(Z), 14(Z)-dienoic acid, to enhance survival and protect against apoptosis in BPAECs stressed with serum starvation. 20-HETE produced a concentration-dependent increase in numbers of starved BPAECs and increased 5-bromo-2'-deoxyuridine incorporation. Caspase-3 activity, nuclear fragmentation studies, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays supported protection from apoptosis and enhanced survival of starved BPAECs treated with a single application of 20-HETE. Protection from apoptosis depended on intact NADPH oxidase, phosphatidylinositol 3 (PI3)-kinase, and ROS production. 20-HETE-stimulated ROS generation by BPAECs was blocked by inhibition of PI3-kinase or Akt activity. These data suggest 20-HETE-associated protection from apoptosis in BPAECs required activation of PI3-kinase and Akt and generation of ROS. 20-HETE also protected against apoptosis in BPAECs stressed by lipopolysaccharide, and in mouse PAs exposed to hypoxia reoxygenation ex vivo. In summary, 20-HETE may afford a survival advantage to BPAECs through activation of prosurvival PI3-kinase and Akt pathways, NADPH oxidase activation, and NADPH oxidase-derived superoxide.