Insight into the Molecular Signature of Skeletal Muscle Characterizing Lifelong Football Players.

BACKGROUND: Aging and sedentary behavior are independent risk factors for non-communicable diseases. An active lifestyle and structured physical activity are positively associated with a healthier quality of life in the elderly. Here, we explored the proteomic/metabolomic muscular signature induced by lifelong football training associated with successful aging. METHODS: The study was performed on nine lifelong football players (67.3 ± 2.8 yrs) and nine aged-matched untrained subjects. We performed a proteomic/metabolomic approach on V. lateralis muscle biopsies; the obtained data were analyzed by means of different bioinformatic tools. RESULTS: Our results indicated that lifelong football training is able to enhance the muscles' oxidative capacity in the elderly by promoting fatty acids as preferential energetic substrates and hence determining a healthier body composition and metabolic profile; furthermore, we showed that the total polyamine content is higher in lifelong football players' muscle, enforcing the involvement of polyamines in muscle growth and hypertrophy. CONCLUSIONS: Lifelong football training, as a structured physical activity, significantly influences the expression of the proteins and metabolites involved in oxidative metabolism and muscle hypertrophy associated with successful aging.

Nano-bio interface between human plasma and niosomes with different formulations indicates protein corona patterns for nanoparticle cell targeting and uptake.

Unraveling the proteins interacting with nanoparticles (NPs) in biological fluids, such as blood, is pivotal to rationally design NPs for drug delivery. The protein corona (PrC), formed on the NP surface, represents an interface between biological components and NPs, dictating their pharmacokinetics and biodistribution. PrC composition depends on biological environments around NPs and on their intrinsic physicochemical properties. We generated different formulations of non-ionic surfactant/non-phospholipid vesicles, called niosomes (NIOs), using polysorbates which are biologically safe, cheap, non-toxic and scarcely immunogenic. PrC composition and relative protein abundance for all designed NIOs were evaluated ex vivo in human plasma (HP) by quantitative label-free proteomics. We studied the correlation of the relative protein abundance in the corona with cellular uptake of the PrC-NIOs in healthy and cancer human cell lines. Our results highlight the effects of polysorbates on nano-bio interactions to identify a protein pattern most properly aimed to drive the NIO targeting in vivo, and assess the best conditions of PrC-NIO NP uptake into the cells. This study dissected the biological identity in HP of polysorbate-NIOs, thus contributing to shorten their passage from preclinical to clinical studies and to lay the foundations for a personalized PrC.

Lifelong Football Training: Effects on Autophagy and Healthy Longevity Promotion.

Aging is a physiological process characterized by a progressive decline of biological functions and an increase in destructive processes in cells and organs. Physical activity and exercise positively affects the expression of skeletal muscle markers involved in longevity pathways. Recently, a new mechanism, autophagy, was introduced to the adaptations induced by acute and chronic exercise as responsible of positive metabolic modification and health-longevity promotion. However, the molecular mechanisms regulating autophagy in response to physical activity and exercise are sparsely described. We investigated the long-term adaptations resulting from lifelong recreational football training on the expression of skeletal muscle markers involved in autophagy signaling. We demonstrated that lifelong football training increased the expression of messengers: RAD23A, HSPB6, RAB1B, TRAP1, SIRT2, and HSBPB1, involved in the auto-lysosomal and proteasome-mediated protein degradation machinery; of RPL1, RPL4, RPL36, MRLP37, involved in cellular growth and differentiation processes; of the Bcl-2, HSP70, HSP90, PSMD13, and of the ATG5-ATG12 protein complex, involved in proteasome promotion and autophagy processes in muscle samples from lifelong trained subjects compared to age-matched untrained controls. In conclusion, our results indicated that lifelong football training positively influence exercise-induced autophagy processes and protein quality control in skeletal muscle, thus promoting healthy aging.

miR-650 promotes motility of anaplastic thyroid cancer cells by targeting PPP2CA.

PURPOSE: Aberrant expression of miRNAs is crucial in several tissues tumorigenesis including thyroid. Recent studies demonstrated that miR-650 plays different role depending on the cancer type. Herein, we investigated the role of miR-650 in thyroid carcinoma. METHODS: The expression of miR-650 was analyzed in human thyroid tissues by q-RT-PCR. Anaplastic (8505C, CAL62, SW1736) and papillary (TPC-1) thyroid cancer cell lines were used to dissect the role of miR-650 on malignant hallmarks of transformation. Label-free proteomic analysis was exploited to unravel the targets of miR-650, while luciferase reporter assay and functional experiments were performed to confirm a selected target. Spearman's rank correlation test was used to assess the association between miR-650 and its target in human thyroid cancer tissues. RESULTS: miR-650 is over-expressed in anaplastic (ATC) thyroid carcinoma where it enhances cell migration and invasion. Proteomic label-free and bioinformatics analysis revealed that the serine-threonine protein phosphatase 2 catalytic subunit alpha (PPP2CA) is a target of miR-650; these finding were confirmed by luciferase assay. Restoration of PPP2CA mRNA, deprived of its 3'UTR, is able to revert the malignant phenotype induced by miR-650 in HEK-293 cells. Importantly, PPP2CA is down-regulated in ATC tissues and is inversely correlated with miR-650. CONCLUSIONS: miR-650 displayed oncogenic activity in ATC cells through targeting PPP2CA phosphatase. These results suggest that miR-650/PPP2CA axis could be modulated to interfere with motile ability of thyroid carcinoma cells.

Protein-protein interaction networks as a new perspective to evaluate distinct functional roles of voltage-dependent anion channel isoforms.

Voltage-dependent anion channels (VDACs) are a family of three mitochondrial porins and the most abundant integral membrane proteins of the mitochondrial outer membrane (MOM). VDACs are known to be involved in metabolite/ion transport across the MOM and in many cellular processes ranging from mitochondria-mediated apoptosis to the control of energy metabolism, by interacting with cytosolic, mitochondrial and cytoskeletal proteins and other membrane channels. Despite redundancy and compensatory mechanisms among VDAC isoforms, they display not only different channel properties and protein expression levels, but also distinct protein partners. Here, we review the known protein interactions for each VDAC isoform in order to shed light on their peculiar roles in physiological and pathological conditions. As proteins associated with the MOM, VDAC opening/closure as a metabolic checkpoint is regulated by protein-protein interactions, and is of pharmacological interest in pathological conditions such as cancer. The interactions involving VDAC1 have been characterized more in depth than those involving VDAC2 and VDAC3. Nevertheless, the so far explored VDAC-protein interactions for each isoform show that VDAC1 is mainly involved in the maintenance of cellular homeostasis and in pro-apoptotic processes, whereas VDAC2 displays an anti-apoptotic role. Despite there being limited information on VDAC3, this isoform could contribute to mitochondrial protein quality control and act as a marker of oxidative status. In pathological conditions, namely neurodegenerative and cardiovascular diseases, both VDAC1 and VDAC2 establish abnormal interactions aimed to counteract the mitochondrial dysfunction which contributes to end-organ damage.

A Functional Interplay between IGF-1 and Adiponectin.

A functional relationship is suggested between two well-known protein hormones, insulin-like growth factor 1 (IGF-1) and adiponectin. In the last two decades in fact, different experimental evidence has indicated a non-random link between them. Here, we describe briefly the IGF-1 and adiponectin systems, and we then focus on their putative interplay in relation to several pathological conditions, including obesity, diabetes, insulin resistance, cardiovascular disease, and cancer. Although the existing studies are hardly comparable, they definitely indicate a functional connection between these two protein hormones. In conclusion, the current knowledge strongly encourages further research into the common, as well as novel, mechanisms through which IGF-1 and adiponectin exert their concerted action.