Adaptive responses of heart and skeletal muscle to spermine oxidase overexpression: Evaluation of a new transgenic mouse model

Roberta Ceci, Guglielmo Duranti, Alessia Leonetti, Stefano Pietropaoli, Federico Spinozzi, Lucia Marcocci, Roberto Amendola, Francesco Cecconi, Stefania Sabatini, Paolo Mariottini, Manuela Cervelli

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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.
Original languageEnglish
Pages (from-to)216 - 225
Number of pages10
JournalFree Radical Biology and Medicine
Volume103
DOIs
Publication statusPublished - 1 Feb 2017
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Ceci, R., Duranti, G., Leonetti, A., Pietropaoli, S., Spinozzi, F., Marcocci, L., Amendola, R., Cecconi, F., Sabatini, S., Mariottini, P., & Cervelli, M. (2017). Adaptive responses of heart and skeletal muscle to spermine oxidase overexpression: Evaluation of a new transgenic mouse model. Free Radical Biology and Medicine, 103, 216 - 225. https://doi.org/10.1016/j.freeradbiomed.2016.12.040