title: Haptoglobin is required to prevent oxidative stress and muscle atrophy.
abstract: BACKGROUND
  Oxidative stress (OS) plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp) is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function. Hp is induced in pro-oxidative conditions such as systemic inflammation or obesity. The role of systemic factors that modulate oxidative stress inside muscle cells is still poorly investigated.
  
  
  RESULTS
  We used Hp knockout mice (Hp-/-) to determine the role of this protein and therefore, of systemic OS in maintenance of muscle mass and function. Absence of Hp caused muscle atrophy and weakness due to activation of an atrophy program. When animals were stressed by acute exercise or by high fat diet (HFD), OS, muscle atrophy and force drop were exacerbated in Hp-/-. Depending from the stress condition, autophagy-lysosome and ubiquitin-proteasome systems were differently induced.
  
  
  CONCLUSIONS
  Hp is required to prevent OS and the activation of pathways leading to muscle atrophy and weakness in normal condition and upon metabolic challenges.
authors: Department of Biomedical Sciences, University of Padova, Padova, Italy; Dulbecco Telethon Institute at Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Enrico
authors: E
authors: Bertaggia
authors: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors: Gaia
authors: G
authors: Scabia
authors: Unit of Neurorehabilitation, Department of Neuroscience, University Hospital of Pisa, Pisa, Italy.
authors: Stefania
authors: S
authors: Dalise
authors: Department of Biomedical Sciences, University of Padova, Padova, Italy; Dulbecco Telethon Institute at Venetian Institute of Molecular Medicine, Padova, Italy.
authors: Francesca
authors: F
authors: Lo Verso
authors: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors: Ferruccio
authors: F
authors: Santini
authors: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors: Paolo
authors: P
authors: Vitti
authors: Unit of Neurorehabilitation, Department of Neuroscience, University Hospital of Pisa, Pisa, Italy.
authors: Carmelo
authors: C
authors: Chisari
authors: Department of Biomedical Sciences, University of Padova, Padova, Italy; Dulbecco Telethon Institute at Venetian Institute of Molecular Medicine, Padova, Italy; CNR Institute of Neuroscience, Padova, Italy; Telethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy.
authors: Marco
authors: M
authors: Sandri
authors: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; CNR Institute of Clinical Physiology, Pisa, Italy.
authors: Margherita
authors: M
authors: Maffei
mesh_terms: D000818:Animals; D001343:Autophagy; D059305:Diet, High-Fat; D015870:Gene Expression; D006242:Haptoglobins / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes; D008297:Male; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D009133:Muscular Atrophy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D006242:Haptoglobins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex