Daniele Capitanio's research while affiliated with University of Milan and other places

Publications (70)

Article
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BMD is characterized by a marked heterogeneity of gene mutations resulting in many abnormal dystrophin proteins with different expression and residual functions. The smaller dystrophin molecules lacking a portion around exon 48 of the rod domain, named the D8 region, are related to milder phenotypes. The study aimed to determine which proteins migh...
Article
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Sphingolipids (SLs) are structural components of the lipid bilayer regulating cell functions. In biological fluids, their distribution is sex-specific and is at variance in aging and many disorders. The aim of this study is to identify SL species associated with the decelerated aging of centenarians. SLs, extracted from serum of adults (Ad, 35-37 y...
Article
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Hypermobile Ehlers-Danlos syndrome (hEDS) is the most frequent type of EDS and is characterized by generalized joint hypermobility and musculoskeletal manifestations which are associated with chronic pain, and mild skin involvement along with the presence of more than a few comorbid conditions. Despite numerous research efforts, no causative gene(s...
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The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient’s outcome is poorly understood. The present study targets the sphingolipid profile of twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry a...
Article
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Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disease, causing motor and cognitive dysfunction and dementia. iNPH and Alzheimer’s disease (AD) share similar molecular characteristics, including amyloid deposition, t-tau and p-tau dysregulation; however, the disease is under-diagnosed and under-treated. The...
Article
Duchenne muscular dystrophy (DMD) causes progressive skeletal muscle degeneration and currently there are few therapeutic options. The identification of new drug targets and their validation in model systems of DMD could be a promising approach to make progress in finding new treatments for this lethal disease. Histone deacetylases (HDACs) play key...
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Obesity is a chronic, complex pathology associated with a risk of developing secondary pathologies, including cardiovascular diseases, cancer, type 2 diabetes (T2DM) and musculoskeletal disorders. Since skeletal muscle accounts for more than 70% of total glucose disposal, metabolic alterations are strictly associated with the onset of insulin resis...
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Mutations in the acidic alpha-glucosidase (GAA) coding gene cause Pompe disease. Late-onset Pompe disease (LOPD) is characterized by progressive proximal and axial muscle weakness and atrophy, causing respiratory failure. Enzyme replacement therapy (ERT), based on recombinant human GAA infusions, is the only available treatment; however, the effica...
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Increased oxidative stress by reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major determinant of disuse-induced muscle atrophy. Muscle biopsies (thigh vastus lateralis, VL) obtained from healthy male subjects enrolled in the Toulouse Cocktail bedrest (BR) study were used to assess efficacy of an antioxidant cocktail (polyph...
Article
Hypermobile Ehlers-Danlos syndrome (hEDS), mainly characterized by generalized joint hypermobility and its complications, minor skin changes, and apparently segregating with an autosomal dominant pattern, is still without a known molecular basis. Hence, its diagnosis is only clinical based on a strict set of criteria defined in the revised EDS noso...
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Aging is characterized by increase in reactive oxygen (ROS) and nitrogen (RNS) species, key factors of cardiac failure and disuse-induced muscle atrophy. This study focused on serum nitroproteome as a trait of longevity by adopting two complementary gel-based techniques: two-dimensional differential in gel electrophoresis (2-D DIGE) and Nitro-DIGE...
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One of the major causes of prosthetic joint failure is infection. Recently, coagulase negative Staphylococcus epidermidis has been identified as an emergent, nosocomial pathogen involved in subclinical prosthetic joint infections (PJIs). The diagnosis of PJIs mediated by S. epidermidis is usually complex and difficult due to the absence of acute cl...
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
Noonan syndrome (NS) is an autosomal-dominant disorder with variable expressivity and locus heterogeneity. Despite several RAS pathway genes were implicated in NS, 20–30% of patients remain without molecular diagnosis, suggesting the involvement of further genes or multiple mechanisms. Eight patients out of 60, negative for conventional NS mutation...
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are characterized by muscle wasting leading to loss of ambulation in the first or third decade, respectively. In DMD, the lack of dystrophin hampers connections between intracellular cytoskeleton and cell membrane leading to repeated cycles of necrosis and regenerati...
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Recent studies on Saudi Arabians indicate a prevalence of dyslipidemia and vitamin D deficiency (25(OH)D) in both normal weight and obese subjects. In the present study the sphingolipid pattern was investigated in 23 normolipidemic normal weight (NW), 46 vitamin D deficient dyslipidemic normal weight (-vitDNW) and 60 vitamin D deficient dyslipidemi...
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Sarcopenia, the progressive loss of muscle mass and strength, is one of the major health issues in older adults, given its high prevalence accompanied by huge clinical and socioeconomic implications. Age-related changes in skeletal muscle can be attributed to mechanisms both directly and indirectly related to muscle homeostasis. Indeed, a wide spec...
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Recent studies on Andean children indicate a prevalence of dyslipidemia and hypertension compared to dwellers at lower altitudes, suggesting that despite similar food intake and daily activities, they undergo different metabolic adaptations. In the present study, the sphingolipid pattern was investigated in serum of 7 underweight (UW), 30 normal we...
Article
Tumor extracellular matrix (ECM) plays a pivotal role in outcome of breast cancer (BC) patients. Overespression of 58 genes, encoding 43 structural ECM proteins, has been identified to determine a specific cluster of BC with accelerated metastatic potential only in the undifferentiated (grade III) phenotype. The scope of this study was to character...
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Idiopathic normal pressure hydrocephalus (iNPH) is characterized by reversible neurological symptoms due to an impairment in cerebrospinal fluid (CSF) clearance. In these patients, cognitive functions are severely impaired, with a scenario similar to Alzheimer's disease (AD), making the differential diagnosis difficult and highlighting the need of...
Chapter
Two-dimensional difference gel electrophoresis (2-D DIGE) is an advanced and elegant gel electrophoretic analytical tool for comparative protein assessment. It is based on two-dimensional gel electrophoresis (2-DE) separation of fluorescently labeled protein extracts. The tagging procedures are designed to not interfere with the chemical properties...
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In mammals, hypoxic stress management is under the control of the Hypoxia Inducible Factors, whose activity depends on the stabilization of their labile α subunit. In particular, the skeletal muscle appears to be able to react to changes in substrates and O2 delivery by tuning its metabolism. The present study provides a comprehensive overview of s...
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Collagen VI is an extracellular matrix (ECM) protein playing a key role in skeletal muscles and whose deficiency leads to connective tissue diseases in humans and in animal models. However, most studies have been focused on skeletal muscle features. We performed an extensive proteomic profiling in two skeletal muscles (diaphragm and gastrocnemius)...
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Obesity is a pathological condition caused by genetic and environmental factors, including vitamin D deficiency, which increases the risk of developing cardiovascular disorders and diabetes. This case-control study was designed to verify whether serum profiles could be identified differentiating obese and non-obese Saudis characterized by vitamin D...
Article
This study utilized 2D-DIGE, isotope-coded protein labelling (ICPL) and biochemical assays to characterize protein alteration in Ulcerative Colitis (UC) and Crohn's Disease (CD) in human epithelial cell and mucosal biopsies in Inflammatory Bowel Disease (IBD)-affected patients. The aim of this study is to identify the key molecular signatures invol...
Article
Introduction: Human skeletal muscle represents 40% of our body mass and deciphering its proteome composition to further understand mechanisms regulating muscle function under physiological and pathological conditions has proved a challenge. The inter-individual variability, the presence of structurally and functionally different muscle types and th...
Data
proApo A-1 proteoforms identification. Representative MS spectrum of proapolipoprotein A-1 proteoforms (upper panel). The N-terminal peptide DEPPQSPWDR, characteristic of Apo A-1 proteoforms, is absent (closeup in the lower panel). (DOCX)
Article
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In the diagnosis of Alzheimer’s disease (AD) total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and the 42 amino acid isoform of alpha β-amyloid (Aβ) are well established surrogate CSF markers. However, there is a constant need for new diagnostic markers to identify the disease at a very early stage. The identification of new molecu...
Data
Data used for AD CSF vs iNPH CSF comparison. Area values used by ClinProTools software to perform statistics on Apo A-1 peak in the comparison AD CSF vs iNPH CSF. The indicated values originates from normalization and smoothing operations performed by the software. (XLSX)
Data
2-D DIGE volumes for Apo A-1 proteoforms in CSF. Values represent the "standardised spot abundances" calculated by DeCyder software. (PDF)
Data
Apo A-1 identification data. Apo A-1 identification results provided by PMF approach. (PDF)
Data
2-D DIGE volumes for Apo A-1 proteoforms in serum. Values represent the "standardised spot abundances" calculated by DeCyder software. (PDF)
Data
Mass spectrometry identification data for apo A-1 and proapo A-1 proteoforms. Together with proteoform name, the GI, therotichal pI and MW, method of analysis, sequence coverage, number of identified peptides and information about MS/MS analysis (where needed) are reported. In proapo proteoforms the N-terminal peptide characteristic of apo proteofo...
Data
Apo A-1 proteoforms identification. In the upper panel the representative MS spectrum of Apolipoprotein A-1 proteoforms with the characteristic N-terminal peptide DEPPQSPWDR at m/z 1226.547 indicated with the arrow. In lower panel the MS/MS spectrum of the peak with m/z 1226.547 is shown. (DOCX)
Data
Apo A-1 identification. The spectrum of apolipoprotein A-1 was obtained after SDS-PAGE and PMF analysis of CSF. (DOCX)
Data
Detailed participants’ characteristics. (PDF)
Data
Data used for AD serum vs iNPH serum vs control serum comparison. Area values used by ClinProTools software to perform statistics on Apo A-1 peak in the comparison AD serum vs iNPH serum vs control serum. The indicated values originate from normalization and smoothing operations performed by the software. (XLSX)
Article
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Aging is a universal phenomenon involving the whole body and is characterized by metabolic and physiological decline, leading to cardiovascular defects and heart failure. To characterize the molecular basis of physiological cardiac aging, the proteomic profiles of Sprague Dawley rat hearts of 6, 22 and 30 months were analysed by DIGE and immunoblot...
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Collagen VI myopathies are genetic disorders due to mutations in collagen 6 A1, 2, and 3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem Myopathy, which is recapitulated by collagen VI null (Col6a1−/−) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of col...
Article
In the skeletal muscle, the ageing process is characterized by a loss of muscle mass and strength, coupled with a decline of mitochondrial function and a decrease of satellite cells. This profile is more pronounced in hindlimb than in forelimb muscles, both in humans and in rodents. Utilizing light and electron microscopy, myosin heavy chain isofor...
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Glioblastoma multiforme is the most aggressive astrocytoma characterized by development of resistant cells to various cytotoxic stimuli. Nitric oxide (NO) is able to overcome tumors resistance in PTEN mutated rat C6 glioma cells due to its ability to inhibit cell growth by influencing the intracellular distribution of ceramide. The aim of this stud...
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This study employed differential proteomic and immunoassay techniques to elucidate the biochemical mechanisms utilized by human muscle (vastus lateralis) in response to high altitude hypoxia exposure. Two groups of subjects, participating in a medical research expedition (A, n = 5, 19d at 5300m altitude; B, n = 6, 66d up to 8848m) underwent a ≈ 30%...
Article
Mutations in the collagen VI genes cause the Ullrich congenital muscular dystrophy (UCMD), with severe phenotype, and Bethlem myopathy (BM) with mild to moderate phenotype. Both, UCMD and BM patients show dystrophic features with degeneration/regeneration and replacement of muscle with fat and fibrous connective tissue. At molecular level, UCMD pat...
Article
Glycosphingolipids (GSLs) are a class of ubiquitous lipids characterized by a wide structural repertoire and a variety of functional implications. Importantly, altered levels have been correlated with different diseases, suggesting their crucial role in health. Conventional methods for the characterization and quantification are based on HPTLC sepa...
Data
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Mass spectrometry data. Protein identification in muscle tissue by PMF and MS/MS. The spot number, the protein names, the gene name, the % of spot variation and the AC number together with MS data are listed. (PDF)
Data
Validation of LC/MS/MS identified proteins by immunoblotting. Immunoblotting of selected proteins (identified with proteomic) in gastrocnemius (A), tibialis anterior (B) and diaphragm (C) muscles from Col6a1−/− versus wild-type pooled samples, normalized against β-tubulin (β-Tub). Pkm2: pyruvate kinase isozymes M1/M2; Vdac1: voltage-dependent anion...
Data
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Supplementary MS data. Representative MALDI-ToF PMF spectra and MSMS sequence analysis from the fragmentation of a precursor ion of identified spots by MALDI-ToF/ToF mass spectrometer. (PDF)
Data
Representative skeletal muscle 2D map. Proteins separation was performed on pH 3–10 NL 24 cm IPG strips in the first dimension and on 12%T-2.5%C PAGE gels in the second dimension. The identified and statistically changed spots in gastrocnemius, tibialis anterior and diaphragm of Col6a1−/− vs. wild-type mice are indicated by numbers. The protein nam...
Article
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This study identifies metabolic and protein phenotypic alterations in gastrocnemius, tibialis anterior and diaphragm muscles of Col6a1(-/-) mice, a model of human collagen VI myopathies. All three muscles of Col6a1(-/-) mice show some common changes in proteins involved in metabolism, resulting in decreased glycolysis and in changes of the TCA cycl...
Data
Myosin heavy chain isoforms composition. SDS electrophoresis was performed on muscle samples using a discontinuous buffer system with a 4% stacking gel (pH 6.8) and a 37% glycerol, 6%T constant concentration running gel (pH 8.8). Samples were separated at 100 V, overnight. Gels were stained with SYPRO Orange (Molecular Probe) and scanned using a 57...
Data
Histograms of proteomics results of stress proteins and others. Histograms of stress proteins and others differentially expressed in gastrocnemius (black bars), tibialis anterior (grey bars) and diaphragm (white bars) muscles. Isoforms of proteins significantly altered (Student’s t-test, p<0.01) are expressed as percent of spot volume variation in...
Data
Schematic representation of the different α-ketoglutarate fate in muscles from Col6a1−/− mice. The direction of IDH1 reaction is controlled by alterations in TCA cycle fluxes leading to the production of anabolic substrates for gastrocnemius and tibialis anterior muscles (panel A), and lipotoxicity for diaphragm muscle (panel B). (TIF)
Article
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Aims: This study utilized proteomics, biochemical and enzymatic assays, and bioinformatics tools that characterize protein alterations in hindlimb (gastrocnemius) and forelimb (triceps) muscles in an amyotrophic lateral sclerosis (ALS) (SOD1(G93A)) mouse model. The aim of this study was to identify the key molecular signatures involved in disease...
Article
Recent studies revealed a key role of mitochondria in the 'axis of aging'. Mitochondrial dysfunction induces ROS production, leading to genotoxic damage, increasing erosion of telomeres followed by the activation of p53, blocking the mitochondrial biogenesis and generating a vicious cycle which induces the age-related mitochondrial dysfunction. Thi...
Article
Exploring cellular mechanisms underlying beneficial and detrimental responses to hypoxia represents the object of the present study. Signaling molecules controlling adaptation to hypoxia (HIF-1α), energy balance (AMPK), mitochondrial biogenesis (PGC-1α), autophagic/apoptotic processes regulation and proteomic dysregulation were assessed. Responses...
Article
The present investigation, the first in the field, was aimed at analyzing differentially, on individual samples, the effects of 55 days of horizontal bed rest, a model for microgravity, on myosin heavy and myosin light chain isoforms distribution (by SDS) and on the proteome (by 2-D DIGE and MS) in the vastus lateralis (VL), a mixed type II/I ($50:...
Article
The present investigation, the first in the field, was aimed at analyzing differentially, on individual samples, the effects of 55 days of horizontal bed rest, a model for microgravity, on myosin heavy and myosin light chain isoforms distribution (by SDS) and on the proteome (by 2-D DIGE and MS) in the vastus lateralis (VL), a mixed type II/I (∼50:...
Article
Recent advances in stem cell biology have demonstrated that terminally differentiated adult cells can be induced to de-differentiate into progenitor cells (induced stem cells) upon proper stimuli. This has been achieved by the induced expression of key regulatory genes by retro- or lenti-viral systems. On the other hand, synthetic "small molecules"...
Article
Ageing induces a progressive morphological change and functional decline in muscles and in nerves. Light and electron microscopy, 2-D DIGE and MS, were applied to profile the qualitative and quantitative differences in the proteome and morphology of rat gastrocnemius muscle and sciatic nerve, in healthy 22-month-old rats. At muscle level, morpholog...
Article
High altitude hypoxia is a paraphysiological condition triggering redox status disturbances of cell organization leading, via oxidative stress, to proteins, lipids, and DNA damage. In man, skeletal muscle, after prolonged exposure to hypoxia, undergoes mass reduction and alterations at the cellular level featuring a reduction of mitochondrial volum...