Exposure of differentiated airway smooth muscle cells to serum stimulates both induction of hypoxia-inducible factor-1{alpha} and airway responsiveness to ACh

• Published in: American journal of physiology. Lung cellular and molecular physiology 2007-10, Vol.293 (4), p.L913
• Main Authors: Chachami, Georgia, Hatziefthimiou, Apostolia, Liakos, Panagiotis, Ioannou, Maria G, Koukoulis, Georgios K, Bonanou, Sofia, Molyvdas, Paschalis-Adam, Simos, George, Paraskeva, Efrosyni
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Airway systems; Animals; Cattle - embryology; Cell Differentiation; Cells, Cultured; Cellular biology; Cobalt; Cobalt - pharmacology; Drug Stability; Drug Synergism; Fetal Blood; Genotype & phenotype; Hypoxia; Hypoxia-Inducible Factor 1 - biosynthesis; Hypoxia-Inducible Factor 1 - chemistry; In Vitro Techniques; Muscle, Smooth - metabolism; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - metabolism; Myosin Heavy Chains - metabolism; Neurotransmitters; Phosphatidylinositol 3-Kinases - metabolism; Protein Biosynthesis - physiology; Rabbits; Reactive Oxygen Species - metabolism; Serum; Signal Transduction - physiology; Trachea - cytology; Trachea - drug effects; Trachea - metabolism; Transcription, Genetic - physiology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00459.2006

Departments of 1 Physiology, 2 Biochemistry, and 3 Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Thessaly, Greece Submitted 20 November 2006 ; accepted in final form 16 July 2007 Airway smooth muscle (ASM) cells are characterized by phenotypic plasticity and can switch between differentiated and proliferative phenotypes. In rabbit tracheal ASM cells that had been differentiated in vitro by serum starvation, readdition of FBS caused initiation of proliferation and induction of nuclear and transcriptionally active hypoxia-inducible factor (HIF)-1 . In addition, FBS stimulated the induction of HIF-1 by the hypoxia mimetic cobalt. Treatment with actinomycin D, cycloheximide, the phosphatidylinositol 3-kinase inhibitors LY-294002 and wortmannin or the reactive oxygen species scavenger diphenyleneiodonium inhibited the FBS-dependent induction of HIF-1 . These data indicate that, in differentiated ASM cells, FBS upregulates HIF-1 by a transcription-, translation-, phosphatidylinositol 3-kinase-, and reactive oxygen species-dependent mechanism. Interestingly, addition of FBS and cobalt also induced HIF-1 in organ cultures of rabbit trachea strips and synergistically increased their contractile response to ACh, suggesting that HIF-1 might be implicated in airway hypercontractility. cobalt; fetal bovine serum Address for reprint requests and other correspondence: E. Paraskeva or G. Simos, Papakiriazi 22, 41222 Larissa, Greece (e-mail: fparaskeva{at}med.uth.gr )