title: PGC-1α plays a major role in the anti-apoptotic effect of 15-HETE in pulmonary artery endothelial cells.
abstract: Peroxisome proliferator activated receptor gamma coactivator 1α (PGC-1α) has been confirmed as a key regulatory factor in pulmonary artery smooth muscle cells to mediate mitochondrial biogenesis and proliferation during hypoxia. However, the functional role of PGC-1α in hypoxic pulmonary artery endothelial cells (PAECs) still needs to be determined. In the present study, we found a marked elevation in the expression of PGC-1α under hypoxia, which was predominate in the nucleus of PAECs. This alteration of PGC-1α showed a significant association with 15-Hydroxyeicosatetraenoic acid (15-HETE), a regulator known to be protective against apoptosis at the concentration of 1 μM. By silencing PGC-1α, the action against cell viability suppression induced by 15-HETE was blocked, not only in normoxic condition but also in hypoxia-stimulated condition. Likewise, the tendency to reduce TUNEL-positive cells, abnormal nuclei and apoptotic cells in response to 15-HETE was depending on PGC-1α. Furthermore, 15-HETE and PGC-1α siRNA caused significant alterations in related mechanisms including caspase activity, mitochondrial membrane potential, and Bcl-2 expression. Taken together, these results provide the first evidence to confirm the importance of PGC-1α in mediating the protective effect of 15-HETE against apoptosis. Therefore, a clear role of PGC-1α in hypoxic PAECs is demonstrated, which may be attributed to pulmonary vascular remodeling.
authors.affiliation: Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China; Department of Biopharmaceutical Sciences, Harbin Medical University -Daqing, Daqing, Heilongjiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China; Department of Biopharmaceutical Sciences, Harbin Medical University -Daqing, Daqing, Heilongjiang, China.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China; Department of Biopharmaceutical Sciences, Harbin Medical University -Daqing, Daqing, Heilongjiang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China; Department of Biopharmaceutical Sciences, Harbin Medical University -Daqing, Daqing, Heilongjiang, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Shen
authors.affiliation: Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China; Department of Biopharmaceutical Sciences, Harbin Medical University -Daqing, Daqing, Heilongjiang, China.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutical Sciences, Harbin Medical University -Daqing, Daqing, Heilongjiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China; Department of Biopharmaceutical Sciences, Harbin Medical University -Daqing, Daqing, Heilongjiang, China. Electronic address: dalingz@yahoo.com.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002417:Cattle; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism*; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D034741:RNA, Small Interfering; D014157:Transcription Factors; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid
keywords: 15-HETE; Apoptosis; Hypoxia; PGC-1α; Pulmonary artery endothelial cells