Hypoxia adaptation in human and animal models: contribution of proteomics

The exploration of cellular mechanisms underlying beneficial adaptive processes and detrimental responses to hypoxia represents the object of several current research studies leading to increase knowledge and possibly modulate or develop new treatments for human diseases. Proteome analysis on skeletal muscles represents a tool for profiling molecular changes leading to adaptation to hypoxia in physiological conditions. Muscles from animal models exposed to acute and prolonged hypoxia, human muscles biopsies from individuals at sea level and at high altitude after nine days, two weeks and after fifty days of exposure were utilized to investigate the alteration occurring in skeletal muscle proteome. The aim was, by characterizing the muscle proteome, to identify cellular processes involved in hypoxia adaptation. Proteome analysis was performed utilizing 2D-DIGE and MALDI-ToF /ToF mass spectrometry. 2D-DIGE analysis revealed that the majority of changed proteins is represented by metabolic enzymes belonging to glycolysis, tricarboxylic acid cycle, fatty acid beta oxidation and oxidative phosphorylation, and by proteins involved in the regulation of protein translation. All these proteins were considerably less abundant under hyoxia versus normoxia. Among proteins involved in stress response a down-regulation in the early fase and an up-regulation of some antioxidant enzymes in the long term exposure were identified. A marked modulation was present also in cytoskeletal and contractile proteins. In addition markers of autophagy, apoptosis, energy production and mitochondrial biogenesis appeared significantly changed during adaptation. Proteomic analysis provided a clear picture of events occurring in muscle tissue under short and long term hypoxia exposure. Particularly, it allows to underline the more relevant changes at the metabolic, functional and structural level involved in the tissue adaptation at the limit of humans tolerance of O2 deprivation. Aknowledgements. Suppoted by MIUR (grant: FIRBRBRNO7BMCT) and by Associazione Everest-K2-CNR.