title: Protein modulation in mouse heart under acute and chronic hypoxia.
abstract: Exploring cellular mechanisms underlying beneficial and detrimental responses to hypoxia represents the object of the present study. Signaling molecules controlling adaptation to hypoxia (HIF-1α), energy balance (AMPK), mitochondrial biogenesis (PGC-1α), autophagic/apoptotic processes regulation and proteomic dysregulation were assessed. Responses to acute hypoxia (AH) and chronic hypoxia (CH) in mouse heart proteome were detected by 2-D DIGE, mass spectrometry and antigen-antibody reactions. Both in AH and CH, the results indicated a deregulation of proteins related to sarcomere stabilization and muscle contraction. Neither in AH nor in CH the HIF-1α stabilization was observed. In AH, the metabolic adaptation to lack of oxygen was controlled by AMPK activation and sustained by an up-regulation of adenosylhomocysteinase and acetyl-CoA synthetase. AH was characterized by the mitophagic protein Bnip 3 increment. PGC-1α, a master regulator of mitochondrial biogenesis, was down-regulated. CH was characterized by the up-regulation of enzymes involved in antioxidant defense, in aldehyde bio-product detoxification and in misfolded protein degradation. In addition, a general down-regulation of enzymes controlling anaerobic metabolism was observed. After 10 days of hypoxia, cardioprotective molecules were substantially decreased whereas pro-apoptotic molecules increased accompained by down-regulation of specific target proteins.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Milano, Segrate (MI), Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Viganò
authors.forename: Michele
authors.initials: M
authors.lastname: Vasso
authors.forename: Anna
authors.initials: A
authors.lastname: Caretti
authors.forename: Valentina
authors.initials: V
authors.lastname: Bravatà
authors.forename: Laura
authors.initials: L
authors.lastname: Terraneo
authors.forename: Chiara
authors.initials: C
authors.lastname: Fania
authors.forename: Daniele
authors.initials: D
authors.lastname: Capitanio
authors.forename: Michele
authors.initials: M
authors.lastname: Samaja
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gelfi
mesh_terms: D000818:Animals; D017209:Apoptosis; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D003285:Contractile Proteins; D006360:Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020543:Proteome