Biomedical subjects

Beniamina Pacchioni

Publications and source records attributed to Beniamina Pacchioni.

3 recordsLinked to original sources

PubMed2006

Parallel protein and transcript profiles of FSHD patient muscles correlate to the D4Z4 arrangement and reveal a common impairment of slow to fast fibre differentiation and a general deregulation of MyoD-dependent genes.

Here, we present the first study of a human neuromuscular disorder at transcriptional and proteomic level. Autosomal dominant facio-scapulo-humeral muscular dystrophy (FSHD) is caused by a deletion of an integral number of 3.3-kb KpnI repeats inside the telomeric region D4Z4 at the 4q35 locus. We combined a muscle-specific cDNA microarray platform with a proteomic investigation to analyse muscle biopsies of patients carrying a variable number of KpnI repeats. Unsupervised cluster analysis divides patients into three classes, according to their KpnI repeat number. Expression data reveal a transition from fast-glycolytic to slow-oxidative phenotype in FSHD muscle, which is accompanied by a deficit of proteins involved in response to oxidative stress. Besides, FSHD individuals show a disruption in the MyoD-dependent gene network suggesting a coregulation at transcriptional level during myogenesis. We also discuss the hypothesis that D4Z4 contraction may affect in trans the expression of a set of genes involved in myogenesis, as well as in the regeneration pathway of satellite cells in adult tissue. Muscular wasting could result from the inability of satellite cells to successfully differentiate into mature fibres and from the accumulation of structural damages caused by a reactive oxygen species (ROS) imbalance induced by an increased oxidative metabolism in fibres.

Adolescent↗

PubMed2005

Cardiac overexpression of melusin protects from dilated cardiomyopathy due to long-standing pressure overload.

We have previously shown that genetic ablation of melusin, a muscle specific beta 1 integrin interacting protein, accelerates left ventricle (LV) dilation and heart failure in response to pressure overload. Here we show that melusin expression was increased during compensated cardiac hypertrophy in mice subjected to 1 week pressure overload, but returned to basal levels in LV that have undergone dilation after 12 weeks of pressure overload. To better understand the role of melusin in cardiac remodeling, we overexpressed melusin in heart of transgenic mice. Echocardiography analysis indicated that melusin over-expression induced a mild cardiac hypertrophy in basal conditions (30% increase in interventricular septum thickness) with no obvious structural and functional alterations. After prolonged pressure overload (12 weeks), melusin overexpressing hearts underwent further hypertrophy retaining concentric LV remodeling and full contractile function, whereas wild-type LV showed pronounced chamber dilation with an impaired contractility. Analysis of signaling pathways indicated that melusin overexpression induced increased basal phosphorylation of GSK3beta and ERK1/2. Moreover, AKT, GSK3beta and ERK1/2 were hyper-phosphorylated on pressure overload in melusin overexpressing compared with wild-type mice. In addition, after 12 weeks of pressure overload LV of melusin overexpressing mice showed a very low level of cardiomyocyte apoptosis and stromal tissue deposition, as well as increased capillary density compared with wild-type. These results demonstrate that melusin overexpression allows prolonged concentric compensatory hypertrophy and protects against the transition toward cardiac dilation and failure in response to long-standing pressure overload.

Animals↗

PubMed2002

Gene expression profiling in dysferlinopathies using a dedicated muscle microarray.

We have performed expression profiling to define the molecular changes in dysferlinopathy using a novel dedicated microarray platform made with 3'-end skeletal muscle cDNAs. Eight dysferlinopathy patients, defined by western blot, immunohistochemistry and mutation analysis, were investigated with this technology. In a first experiment RNAs from different limb-girdle muscular dystrophy type 2B patients were pooled and compared with normal muscle RNA to characterize the general transcription pattern of this muscular disorder. Then the expression profiles of patients with different clinical traits were independently obtained and hierarchical clustering was applied to discover patient-specific gene variations. MHC class I genes and genes involved in protein biosynthesis were up-regulated in relation to muscle histopathological features. Conversely, the expression of genes codifying the sarcomeric proteins titin, nebulin and telethonin was down-regulated. Neither calpain-3 nor caveolin, a sarcolemmal protein interacting with dysferlin, was consistently reduced. There was a major up-regulation of proteins interacting with calcium, namely S100 calcium-binding proteins and sarcolipin, a sarcoplasmic calcium regulator.

Adolescent↗