title: 15-Hydroxyeicosatetraenoic acid (15-HETE) protects pulmonary artery smooth muscle cells against apoptosis via HSP90.
abstract: OBJECTIVE
  15-Hydroxyeicosatetraenoic acid (15-HETE), generated by hypoxia, is a product of arachidonic acid and mainly catalyzed by 15-lipoxygenase (15-LO) in pulmonary artery. As HSP90 is known to be involved in apoptosis in other tissues and cells, we aim to test whether anti-apoptotic effect of 15-HETE is regulated by the molecular chaperone in pulmonary artery smooth muscle cells.
  
  
  METHODS
  To test this hypothesis, we performed cell viability analysis, mitochondrial potential assay, caspase-3 activity measurement, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling with and without HSP90 inhibitor.
  
  
  RESULTS
  Our results showed that both exogenous and endogenous 15-HETE up-regulated HSP90 expression and prevented PASMC from serum deprivation-induced apoptosis. Serum deprivation lead to mitochondrial membrane depolarization, decreased expression of Bcl-2 and enhanced expression of Bax, and activation of caspase-3 and caspase-9 in PASMCs. 15-HETE reversed all these effects in a HSP90-dependent manner.
  
  
  CONCLUSIONS
  This study establishes the factor involved in 15-HETE-protecting PASMC from apoptosis and the regulation of HSP90 by 15-HETE may be an important mechanism underlying the treatment of pulmonary artery hypertension and provide a novel therapeutic target in future.
authors.affiliation: Institute of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang, Heilongjiang, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Ran
authors.forename: Shulin
authors.initials: S
authors.lastname: Liu
authors.forename: Chun
authors.initials: C
authors.lastname: Jiang
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D053938:DNA Fragmentation; D005786:Gene Expression Regulation; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D006893:Hydroxyeicosatetraenoic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D020169:Caspases