Data on protein abundance alteration induced by chronic exercise in mdx mice model of Duchenne muscular dystrophy and potential modulation by apocynin and taurine

Here we present original data related to the research paper entitled “Proteome analysis in dystrophic mdx mouse muscle reveals a drastic alteration of Key Metabolic and Contractile Proteins after chronic exercise and the potential modulation by anti-oxidant compounds” (Gamberi et al., 2018) [1]. The dystrophin-deficient mdx mouse is the most common animal model for Duchenne muscular dystrophy. The mdx mice phenotype of the disorder is milder than in human sufferers and it can be worsened by chronic treadmill exercise. Apocynin and taurine are two antioxidant compounds proved to be beneficial on some pathology related parameters (Schröder and Schoser, 2009) [2]. This article reports the detailed proteomic data on protein abundance alterations, in tibialis anterior muscle of mdx mice, induced by chronic exercise protocol. A selected group of mdx mice was also treated with apocynin and taurine during this protocol. Detailed MS data, comparison between mdx vs wild type, exercised mdx vs wild type, and complete analysis of spot variation are provided. Furthermore, in wild type mice subjected to the same exercise protocol, the abundance of key proteins, resulted modified in exercised mdx, were analyzed by western blot

Proteome analysis in dystrophic mdx mouse muscle reveals a drastic alteration of key metabolic and contractile proteins after chronic exercise and the potential modulation by anti-oxidant compounds

Weakness and fatigability are typical features of Duchenne muscular dystrophy patients and are aggravated in dystrophic mdx mice by chronic treadmill exercise. In the present study, we describe, the pattern of differentially abundant spots that is associated to the worsening of dystrophy phenotype induced by chronic exercise. Our proteomic analysis pointed out 34 protein spots with different abundance between sedentary and exercised mdx mice. These proteins belong mostly to glucose metabolism, energy production and sarcomere structure categories. Interestingly exercise induced an increase of typical fast twitch fiber proteins (Troponin T fast skeletal muscle, Troponin I fast skeletal muscle and Myozenin-1) combined with an increase of several glycolytic enzymes. Concerning energy transfer, Adenylate kinase, showed a marked decrease when compared with non-exercised mdx. The decline of this enzyme correlates with increased Creatin kinase enzyme, suggesting that a compensatory energy metabolism mechanism could be activated in mdx mouse skeletal muscle following exercise. In addition, we analysed muscles from exercised mdx mice treated with two natural anti-oxidant compounds, apocynin and taurine, that in our previous study, were proved to be beneficial on some pathology related parameters, and we showed that these compounds can counteract exercise-induced changes in the abundance of several proteins. Significance Mdx mouse model of Duchenne muscular dystrophy shows a phenotype of the disorder milder than in human sufferers. This phenotype can be worsened by a different protocols of chronic exercise. These protocols can mimic the muscle progressive damage observed in humans, can allow studying the effects of inadequate training on dystrophic muscles and have been largely used to assess the ability of a drug to reduce the damage induced by exercise. In this study, we describe for the first time, the pattern of protein variation associated with the worsening of dystrophy phenotype induced by chronic exercise. Our proteomic analysis pointed out 34 protein spots with different amount between sedentary and exercised mdx mice. These proteins belong mostly to glucose metabolism, energy production and sarcomere structure categories and their variation indicates that mdx exercised muscle are not able to carry out the metabolic changes associated to fast-to-slow transition typically observed in aerobically trained muscle

Antiproliferative effects of two gold(I)-N-heterocyclic carbene complexes in A2780 human ovarian cancer cells: A comparative proteomic study

Au(NHC) and Au(NHC)2, i.e. a monocarbene gold(I) complex and the corresponding bis(carbene) complex, are two structurally related compounds, endowed with cytotoxic properties against several cancer cell lines. Herein, we explore the molecular and cellular mechanisms at the basis of their cytotoxicity in A2780 human ovarian cancer cells. Through a comparative proteomic analysis, we demonstrated that the number of modulated proteins is far larger in Au(NHC)2- treated than in Au(NHC)-treated A2780 cells. Both gold compounds mainly affected proteins belonging to the following functional classes: protein synthesis, metabolism, cytoskeleton and stress response and chaperones. Particularly, Au(NHC)2gave rise to an evident upregulation of several glycolytic enzymes. Moreover, only Au(NHC)2triggered a net impairment of respiration and a metabolic shift towards glycolysis, suggesting that mitochondria are relevant cellular targets. We also found that both carbenes, similarly to the gold(I) compound auranofin, caused a strong inhibition of the seleno-enzyme thioredoxin reductase (TrxR). In conclusion, we highlighted that coordination of two carbene ligands to the same gold(I) center greatly enhances the antiproliferative effects of the resulting compound in comparison to the monocarbene derivative. Moreover, TrxR inhibition and metabolic impairment seem to play a major role in the Au(NHC)2cytotoxicity. Overall, these antiproliferative effects were also confirmed on other two human ovarian cancer cell lines (i.e. SKOV3 and IGROV1)

Proteomic analysis of the cytotoxic effects induced by the organogold(iii) complex Aubipycin cisplatin-resistant A2780 ovarian cancer cells: further evidence for the glycolytic pathway implication

The cellular alterations produced in cisplatin-resistant A2780 ovarian cancer cells (A2780/R) upon treatment with the cytotoxic organogold(III) complex Aubipyc were investigated in depth through a classical proteomic approach. We observed that A2780/R cell exposure to a cytotoxic concentration of Aubipyc for 24 hours results in a conspicuous number of alterations at the protein level that were carefully examined. Notably, we observed that several affected proteins belong to the glucose metabolism system further supporting the idea that the cytotoxic effects of Aubipyc in A2780/R cells are mostly mediated by an impairment of glucose metabolism in excellent agreement with previous observations on the parent cisplatin-sensitive cell line