Protein modulation in mouse heart under acute and chronic hypoxia

Agnese Viganó, Michele Vasso, Anna Caretti, Valentina Bravatá, Laura Terraneo, Chiara Fania, Daniele Capitanio, Michele Samaja, Cecilia Gelfi

Research output: Contribution to journalArticle

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 upregulation 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 downregulation of specific target proteins.

Original languageEnglish
Pages (from-to)4202-4217
Number of pages16
JournalProteomics
Volume11
Issue number21
DOIs
Publication statusPublished - 2012

    Fingerprint

Keywords

  • AMPK
  • Animal proteomics
  • Apoptosis
  • Autophagy
  • Heart
  • Hypoxia

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Viganó, A., Vasso, M., Caretti, A., Bravatá, V., Terraneo, L., Fania, C., Capitanio, D., Samaja, M., & Gelfi, C. (2012). Protein modulation in mouse heart under acute and chronic hypoxia. Proteomics, 11(21), 4202-4217. https://doi.org/10.1002/pmic.201000804