Sugumaran Praveen Kumar, Wang Shuang, Song Shasha, Nie Xiaowei, Zhang Lei, Feng Ye, Ma Wenchao, Zhu Daling
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Nangang District, Harbin, Heilongjiang 150081, PR China.
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Nangang District, Harbin, Heilongjiang 150081, PR China; Biopharmaceutical Key Laboratory of Heilongjiang Province, 157 Baojian Road, Harbin, Heilongjiang 150081, PR China; Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University-Daqing, Daqing, Heilongjiang province 163319, PR China.
Prostaglandins Leukot Essent Fatty Acids. 2014 Apr;90(4):89-98. doi: 10.1016/j.plefa.2014.01.006. Epub 2014 Feb 10.
Pulmonary arterial hypertension (PAH) is a progressive condition in which remodeling of the pulmonary vasculature plays an important role. The vascular remodeling involves pulmonary arterial smooth muscle cell (PASMC) proliferation and apoptosis, which is affected by several arachidonic acid metabolites. 15-oxo-Eicosatetraenoic acid (15-oxo-ETE) is one of the metabolites. However, the biological role of 15-oxo-ETE in PASMCs remains unknown. Here we show evidence for the modulation of PASMC apoptosis by 15-oxo-ETE. We found that 15-oxo-ETE increased rat and human PASMC viability. Consistently, 15-oxo-ETE attenuated nuclear fragmentation and DNA strand breaks, decreased caspase-3 activity, reduced mitochondrial depolarization, and increased Bcl-2 expression. Interestingly, the anti-apoptotic effect of 15-oxo-ETE was lost when the Akt intracellular signaling pathway was blocked. Taken together, we have established that 15-oxo-ETE protects PASMCs against apoptosis through the Akt pathway. These results suggest that 15-oxo-ETE seems to be a potential agent for PAH controls by preventing unwanted PASMC death.
肺动脉高压（PAH）是一种进行性疾病，其中肺血管重塑起着重要作用。血管重塑涉及肺动脉平滑肌细胞（PASMC）的增殖和凋亡，这受到几种花生四烯酸代谢产物的影响。15-氧代二十碳四烯酸（15-oxo-ETE）是其中一种代谢产物。然而，15-oxo-ETE在PASMC中的生物学作用仍不清楚。在此，我们展示了15-oxo-ETE对PASMC凋亡的调节作用的证据。我们发现15-oxo-ETE提高了大鼠和人类PASMC的活力。一致地，15-oxo-ETE减轻了核碎裂和DNA链断裂，降低了caspase-3活性，减少了线粒体去极化，并增加了Bcl-2表达。有趣的是，当Akt细胞内信号通路被阻断时，15-oxo-ETE的抗凋亡作用丧失。综上所述，我们确定15-oxo-ETE通过Akt途径保护PASMC免受凋亡。这些结果表明，15-oxo-ETE似乎是一种通过防止不必要的PASMC死亡来控制PAH的潜在药物。
