title: Effect of hypoxia on lung gene expression and proteomic profile: insights into the pulmonary surfactant response.
abstract: Exposure of lung to hypoxia has been previously reported to be associated with significant alterations in the protein content of bronchoalveolar lavage (BAL) and lung tissue. In the present work we have used a proteomic approach to describe the changes in protein complement induced by moderate long-term hypoxia (rats exposed to 10% O2 for 72h) in BAL and lung tissue, with a special focus on the proteins associated with pulmonary surfactant, which could indicate adaptation of this system to limited oxygen availability. The analysis of the general proteomic profile indicates a hypoxia-induced increase in proteins associated with inflammation both in lavage and lung tissue. Analysis at mRNA and protein levels revealed no significant changes induced by hypoxia on the content in surfactant proteins or their apparent oligomeric state. In contrast, we detected a hypoxia-induced significant increase in the expression and accumulation of hemoglobin in lung tissue, at both mRNA and protein levels, as well as an accumulation of hemoglobin both in BAL and associated with surface-active membranes of the pulmonary surfactant complex. Evaluation of pulmonary surfactant surface activity from hypoxic rats showed no alterations in its spreading ability, ruling out inhibition by increased levels of serum or inflammatory proteins.
  
  
  CONCLUSIONS
  This work reveals that hypoxia induces extensive changes in the proteomic profile of lung bronchoalveolar lavage, including the presence of proteins related with inflammation both in lung tissue and lavage, and a significant increase in the synthesis and secretion by the lung tissue of different forms of hemoglobin. The level of specific pulmonary surfactant-associated proteins is not substantially altered due to hypoxia, but hypoxia-adapted surfactant exhibits an enhanced ability to form surface-active films at the air-liquid interface. The increased amount of β-globin integrated into the operative surfactant complexes obtained from hypoxic rats is a relevant feature that points to the existence of adaptive responses coupling surfactant function and oxygen availability.
authors.affiliation: Dept. Bioquímica, Fac. Biología, Universidad Complutense, Madrid, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Olmeda
authors.affiliation: Center for Host Defense, Inflammation, and Lung Disease (CHILD), Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Umstead
authors.affiliation: Center for Host Defense, Inflammation, and Lung Disease (CHILD), Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Silveyra
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pascual
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: José
authors.initials: J
authors.lastname: López-Barneo
authors.affiliation: Center for Host Defense, Inflammation, and Lung Disease (CHILD), Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Phelps
authors.affiliation: Center for Host Defense, Inflammation, and Lung Disease (CHILD), Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros
authors.affiliation: Dept. Bioquímica, Fac. Biología, Universidad Complutense, Madrid, Spain. Electronic address: jperezgil@bio.ucm.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez-Gil
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism*; D008055:Lipids / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D020543:Proteome / Q000032:analysis* / Q000187:drug effects* / Q000378:metabolism; D040901:Proteomics; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D051381:Rats
chemical_list: D008055:Lipids; D011506:Proteins; D020543:Proteome; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants
keywords: ABCA3; Air–liquid interface; Hemoglobin; Lung surfactant; Surfactant proteins