title: Hypoxia inhibits pulmonary artery endothelial cell apoptosis via the e-selectin/biliverdin reductase pathway.
abstract: Hypoxia-induced inhibition of apoptosis in pulmonary artery endothelial cells (PAECs) has an important role in pulmonary arterial remodeling leading to aggravated hypoxic pulmonary arterial hypertension. However, the mechanisms involved in the hypoxia-induced inhibition of PAEC apoptosis have not been elucidated. e-selectin and biliverdin reductase (BVR) have been reported to contribute to the cascade of apoptosis in several cell lines but not in PAECs. In the present study, we show that the expression of e-selectin and BVR was both up-regulated by hypoxia in PAECs. Moreover, hypoxia attenuated the decreased cell survival and apoptotic protein expression, and increased DNA fragmentation induced by serum deprivation in the PAECs, which was mediated by the e-selectin/BVR pathway. In addition, by examining the mitochondrial membrane potential and mitochondrial membrane proteins (Bcl-2 and BAX), we show that the mitochondrial-dependent apoptosis pathway was necessary for the e-selectin/BVR pathway inducing the anti-apoptotic effect of hypoxia in PAECs. Taken all together, our data show that the e-selectin/BVR pathway participates in the inhibitory process of hypoxia in PAEC apoptosis which is mediated by the mitochondrial-dependent apoptosis pathway.
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Min
authors.initials: M
authors.lastname: Mao
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Xijuan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China.
authors.forename: Hengyuan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China. Electronic address: dalingz@yahoo.com.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D000860:Hypoxia / Q000201:enzymology* / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000201:enzymology* / Q000473:pathology; D034622:RNA Interference; D017208:Rats, Wistar; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D019040:E-Selectin; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase
keywords: Apoptosis; Biliverdin reductase; Hypoxia; Pulmonary artery endothelial cells; e-selectin