Aims: The result of an imbalance between tissue oxygen supply and demand is a component of cardiovascular diseases. Exploring cellular mechanisms underlying beneficial adaptive processes and detrimental responses during hypoxia exposure represents the object of the present study. An animal model was utilized in order to assess entire proteome changes induced by normobaric acute and chronic hypoxia at the cardiac level. Methods: Male mice were divided into three groups: normoxic mice (N, n=5) that breathed room air (FiO2=0.21), Acute Hypoxia mice (AH, n=5) exposed for 48 hrs to a normobaric hypoxic atmosphere (8% O2, FiO2=0.08), and Chronic Hypoxia mice (CH, n=5) that were subjected to the same treatment as the AH but for 10 days. The hearts were removed soon after the sacrifice and processed for protein extraction. Samples were analyzed by 2D-DIGE coupled with MALDI-ToF mass spectrometry and immunoblotting. Results: Proteomic results showed that a number of cellular processes appeared differently de-regulated in AH and CH: the cytoskeletal contractile machinery, the metabolic and mitochondrial compartment, the stress response system, the machinery of damaged proteins removal as well as iron and coagulation proteins. Immunoblotting assays underlined the involvement of energy utilization control, mitochondrial biogenesis and mitophagy in AH and the appearance of pro-apoptotic molecules in CH. Conclusions: This study combined data provided by proteomic analysis with specific signaling molecules playing a key role in hypoxia adaptation and allowed to profile protein changes in mice cardiac muscle in response to acute and chronic hypoxia. In our model, the cardiac muscle appeared to adapt to 8% of oxygen by controlling metabolism and ROS production in AH and by adopting an active mechanism to counteract damages induced by chronic hypoxia by increasing antioxidant enzymes. Nevertheless, in CH, the tissue was in a critical condition as suggested by the decrement of molecules essential for cell survival and comparison of pro-apoptotic signals. The association of protein changes to upstream regulators of hypoxia adaptation provided a set of molecular variables playing a key role in hypoxia sensing opening new possibilities for prevention and development of therapeutical strategies counteracting negative effects of oxygen lack.
Protein modulation in mouse heart under acute and chronic hypoxia / A. Viganò, M. Vasso, A. Caretti, V. Bravatà, L. Terraneo, C. Fania, D. Capitanio, M. Samaja, C. Gelfi, D. Capitanio. ((Intervento presentato al 18. convegno Congresso nazionale tenutosi a Imola nel 2011.
|Titolo:||Protein modulation in mouse heart under acute and chronic hypoxia|
|Data di pubblicazione:||2011|
|Settore Scientifico Disciplinare:||Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica|
|Enti collegati al convegno:||Società italiana di ricerche cardiovascolari|
|Citazione:||Protein modulation in mouse heart under acute and chronic hypoxia / A. Viganò, M. Vasso, A. Caretti, V. Bravatà, L. Terraneo, C. Fania, D. Capitanio, M. Samaja, C. Gelfi, D. Capitanio. ((Intervento presentato al 18. convegno Congresso nazionale tenutosi a Imola nel 2011.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|