title: 15-oxo-Eicosatetraenoic acid prevents serum deprivation-induced apoptosis of pulmonary arterial smooth muscle cells by activating pro-survival pathway.
abstract: 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.
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Nangang District, Harbin, Heilongjiang 150081, PR China.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Sugumaran
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Nangang District, Harbin, Heilongjiang 150081, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Nangang District, Harbin, Heilongjiang 150081, PR China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Nangang District, Harbin, Heilongjiang 150081, PR China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Nangang District, Harbin, Heilongjiang 150081, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Nangang District, Harbin, Heilongjiang 150081, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Nangang District, Harbin, Heilongjiang 150081, PR China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Ma
authors.affiliation: 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. Electronic address: dalingz@yahoo.com.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001095:Arachidonic Acids / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D001095:Arachidonic Acids; D002867:Chromones; D016895:Culture Media, Serum-Free; D009025:Morpholines; D019253:Proto-Oncogene Proteins c-bcl-2; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C054992:15-keto-5,8,11,13-eicosatetraenoic acid; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: 15-oxo-ETE; Akt; Apoptosis; Pulmonary arterial hypertension; Pulmonary artery smooth muscle cells