Exposure of differentiated airway smooth muscle cells to serum stimulates both induction of hypoxia-inducible factor-1{alpha} and airway responsiveness to ACh.
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)-1alpha. In addition, FBS stimulated the induction of HIF-1alpha 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-1alpha. These data indicate that, in differentiated ASM cells, FBS upregulates HIF-1alpha by a transcription-, translation-, phosphatidylinositol 3-kinase-, and reactive oxygen species-dependent mechanism. Interestingly, addition of FBS and cobalt also induced HIF-1alpha in organ cultures of rabbit trachea strips and synergistically increased their contractile response to ACh, suggesting that HIF-1alpha might be implicated in airway hypercontractility.
Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Thessaly, Greece.
Georgia
G
Chachami
Apostolia
A
Hatziefthimiou
Panagiotis
P
Liakos
Maria G
MG
Ioannou
Georgios K
GK
Koukoulis
Sofia
S
Bonanou
Paschalis-Adam
PA
Molyvdas
George
G
Simos
Efrosyni
E
Paraskeva
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002417:Cattle / Q000196:embryology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D004355:Drug Stability; D004357:Drug Synergism; D005312:Fetal Blood; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis* / Q000737:chemistry; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D044967:Serum; D015398:Signal Transduction / Q000502:physiology; D014132:Trachea / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
D051793:Hypoxia-Inducible Factor 1; D017382:Reactive Oxygen Species; D003035:Cobalt; D019869:Phosphatidylinositol 3-Kinases; D018995:Myosin Heavy Chains; C018021:cobaltous chloride; D000109:Acetylcholine