Exploring cellular mechanisms underlying beneficial adaptive processes and detrimental responses to hypoxia represents the object of the present study. Signaling molecules controlling adaptation to hypoxia (HIF-1), energy balance (AMPK), mitochondrial biogenesis, (PGC-1) and the regulation of autophagic/apoptotic processes, combined with proteomic dysregulation were assessed. Responses to normobaric acute (48 hrs FiO2 = 0.08) and chronic (10 days FiO2 = 0.08) hypoxia in mouse heart proteome were detected applying 2-D DIGE, mass spectrometry and antigen antibody reactions. Both in acute (AH) and chronic (CH) hypoxia, results indicated a deregulation of proteins related to sarcomere stabilization and muscle contraction. Neither in AH nor in CH HIF-1 stabilization was detected. In AH, the metabolic adaptation to oxygen lack is controlled by AMPK activation and sustained by the massive up-regulation of adenosylhomocysteinase and of acetyl coenzyme A synthetase. AH is also characterized by an up-regulation of Bnip 3 which is known to induce mitophagy and decreasing oxidative damage. PGC-1, a master regulator of mitochondrial biogenesis, was down- regulated. CH was characterized by up-regulation of enzymes involved in antioxidant defense, in aldehyde bio-product detoxification and in misfolded protein degradation. In addition, a massive down-regulation of enzymes controlling anaerobic metabolism was observed. After 10 days of hypoxia, cardioprotective molecules were substantially decreased whereas pro-apoptotic signals were correlated with the increment of apoptotic program and sustained by the down-regulation of specific target proteins. In conclusion, differential analysis provided new insight into target molecules sensing lack of oxygen in vivo and could open new possibilities for protection from damages induced by long term hypoxia exposure.
Protein modulation in mouse heart under acute and chronic hypoxia / C. Gelfi, A. Viganò, M. Vasso, D. Capitanio, R. Leone, A. Caretti, M. Samaja. ((Intervento presentato al convegno Basic Cardiovascular Sciences Congress tenutosi a New Orleans nel 2011.
|Titolo:||Protein modulation in mouse heart under acute and chronic hypoxia|
|Data di pubblicazione:||lug-2011|
|Settore Scientifico Disciplinare:||Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica|
|Citazione:||Protein modulation in mouse heart under acute and chronic hypoxia / C. Gelfi, A. Viganò, M. Vasso, D. Capitanio, R. Leone, A. Caretti, M. Samaja. ((Intervento presentato al convegno Basic Cardiovascular Sciences Congress tenutosi a New Orleans nel 2011.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|