title: Adaptive responses of heart and skeletal muscle to spermine oxidase overexpression: Evaluation of a new transgenic mouse model.
abstract: Spermine oxidase oxidizes spermine to produce H2O2, spermidine, and 3-aminopropanal. It is involved in cell drug response, apoptosis, and in the etiology of several pathologies, including cancer. Spermine oxidase is an important positive regulator of muscle gene expression and fiber size and, when repressed, leads to muscle atrophy. We have generated a transgenic mouse line overexpressing Smox gene in all organs, named Total-Smox. The spermine oxidase overexpression was revealed by β-Gal staining and reverse-transcriptase/PCR analysis, in all tissues analysed. Spermine oxidase activity resulted higher in Total-Smox than controls. Considering the important role of this enzyme in muscle physiology, we have focused our study on skeletal muscle and heart of Total-Smox mice by measuring redox status and oxidative damage. We assessed the redox homeostasis through the analysis of the reduced/oxidized glutathione ratio. Chronic H2O2production induced by spermine oxidase overexpression leads to a cellular redox state imbalance in both tissues, although they show different redox adaptation. In skeletal muscle, catalase and glutathione S-transferase activities were significantly increased in Total-Smox mice compared to controls. In the heart, no differences were found in CAT activity level, while GST activity decreased compared to controls. The skeletal muscle showed a lower oxidative damage than in the heart, evaluated by lipid peroxidation and protein carbonylation. Altogether, our findings illustrate that skeletal muscle adapts more efficiently than heart to oxidative stress H2O2-induced. The Total-Smox line is a new genetic model useful to deepen our knowledge on the role of spermine oxidase in muscle atrophy and muscular pathological conditions like dystrophy.
authors.affiliation: Unit of Biology, Genetics and Biochemistry, University of Rome "Foro Italico", Piazza Lauro De Bosis 15, 00135, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ceci
authors.affiliation: Unit of Biology, Genetics and Biochemistry, University of Rome "Foro Italico", Piazza Lauro De Bosis 15, 00135, Rome, Italy.
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Duranti
authors.affiliation: Department of Sciences, Roma Tre Università, 00146, Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Leonetti
authors.affiliation: Department of Sciences, Roma Tre Università, 00146, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pietropaoli
authors.affiliation: Department of Sciences, Roma Tre Università, 00146, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Spinozzi
authors.affiliation: Department of Biochemical Sciences 'A.Rossi Fanelli', La Sapienza University, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Marcocci
authors.affiliation: ENEA, CR Casaccia, BAS.BIOTEC. MED., 00123, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Amendola
authors.affiliation: Department of Biology, University of Rome 'Tor Vergata', 00133, Rome, Italy; Unit of Cell Stress and Survival, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cecconi
authors.affiliation: Unit of Biology, Genetics and Biochemistry, University of Rome "Foro Italico", Piazza Lauro De Bosis 15, 00135, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sabatini
authors.affiliation: Department of Sciences, Roma Tre Università, 00146, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mariottini
authors.affiliation: Department of Sciences, Roma Tre Università, 00146, Rome, Italy. Electronic address: manuela.cervelli@uniroma3.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Cervelli
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D015870:Gene Expression; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism; D000097667:Polyamine Oxidase
chemical_list: D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D000097667:Polyamine Oxidase
keywords: Oxidative stress; Polyamines; Skeletal muscle; Spermine oxidase