Digitum Colección:
http://hdl.handle.net/10201/58703
2024-03-28T18:09:16ZThe peculiar apoptotic behavior of skeletal muscle cells
http://hdl.handle.net/10201/59683
Título: The peculiar apoptotic behavior of skeletal muscle cells
Autor/es principal/es: Salucci, Sara; Burattini, Sabrina; Baldassarri, Valentina
Resumen: Apoptosis plays an active role in maintaining
skeletal muscle homeostasis. Its deregulation is involved
in several skeletal muscle disorders such as dystrophies,
myopathies, disuse and sarcopenia.
The aim of this work was to study in vitro the
apoptotic behavior induced by etoposide, staurosporine
and hydrogen peroxide in the C2C12 skeletal muscle cell
line, comparing myoblast vs myotube sensitivity,
investigated by means of morphological and
cytofluorimetric analyses.
Myotubes appeared more resistant than myoblasts to
apoptotic induction. In myoblasts treated with etoposide,
nuclei with chromatin condensation were observed, in
the presence of a diffuse DNA fragmentation, as shown
by confocal microscopy. The latter also appeared in
myotubes, where apoptotic and normal nuclei coexisted
inside the same syncytium. After staurosporine
treatment, myobalsts evidenced late apoptotic features
and a high number of TUNEL-positive nuclei.
Secondary necrosis appeared in myotubes, where
myonuclei with cleaved DNA again coexisted with
normal myonuclei. After H2O2 exposure, myotubes,
differently from myoblasts, showed a poor sensitivity to
cell death. Intriguingly, autophagic granules appeared
abundantly in myotubes after each treatment. In
myotubes, mitochondria were better preserved than in
myoblasts since those which were damaged were
probably degraded through autophagic processes. These findings demonstrate a scarce sensitivity of
myotubes to apoptotic stimuli due to acquisition of an
apoptosis-resistant phenotype during differentiation. The
presence of nuclear-dependent “territorial” death
domains in the syncytium could explain a slower death
of myotubes compared to mononucleated cells. In
addition, autophagy could preserve and protect muscle cell integrity against chemical stimuli, making C2C12
cells, in particular myotubes, more resistant to apoptosis
induction.2013-01-01T00:00:00ZEffect of regenerative factor rich plasma, P substance and fetal calf serum on the growth of epithelial cells in the cornea. Comparative experimental study
http://hdl.handle.net/10201/59682
Título: Effect of regenerative factor rich plasma, P substance and fetal calf serum on the growth of epithelial cells in the cornea. Comparative experimental study
Autor/es principal/es: Márquez de Aracena del Cid, R.; Pérez Ordoñez, A.
Resumen: Purpose. The goal of this study was to
evaluate the experimental effectiveness of Regenerative
Factor Rich Plasma (RFRP) of human blood versus Fetal
Bovim Serum (FBS) and neuropeptide Substance P (SP)
on corneal epithelium cell proliferation. Method. Rabbit
corneal epithelium cell (CCL-60) growth was compared
between different RFRP fractions, FBS and with the
neuropeptide Substance P. The ability of the RFRP
fractions and SP to revert the inhibitory effect of the CsA
was also evaluated. Results. All groups showed an
increase (p<0.001) in corneal epithelial cell growth
compared with the control group. The maximum
capacity of cell growth was obtained with dilutions of
50% in the FBS, RFRP-I, RFRP -II, RFRP-III groups
and with 100nM of SP. The highest growth was observed
with 50% FBS, RFRP-I and RFRP-II. The group with
SP and RFRP-III had significantly lower growth
(p<0.001). When the NK1 receptor antagonist CsA was
added at a dose of IC50, we found a significant decrease
in cell growth (p<0.001) in all culture conditions,
including the control group. The decrease was similar in
all groups, but was especially pronounced in RFRP-II.
RFRP I, II and III promoted growth more than SFB
10%. Conclusion. The RFRP of human blood promotes
the growth of corneal epithelial cells in a significantly
more efficient manner than FSB and SP. RFRP can be
effective both in cell cultures and stem cell cultures.2013-01-01T00:00:00ZNotch receptors in human choroid plexus tumors
http://hdl.handle.net/10201/59645
Título: Notch receptors in human choroid plexus tumors
Autor/es principal/es: Beschorner, R.; Waidelich, J.; Trautmann, K.; Psaras, T.; Schittenhelm, J.
Resumen: Notch signaling plays a role in development
and formation of the normal choroid plexus (nCP), and
in formation of various tumors in humans. Activation of
Notch3 has been reported to promote tumor growth in
invasive gliomas and to initiate formation of choroid
plexus tumors (CPT) in mice.
We investigated the expression of all currently
known Notch receptors (Notch 1-4) in 55 samples of
nCP and 88 CPT, including 61 choroid plexus
papillomas (CPP), 22 atypical CPP and 5 choroid plexus
carcinomas by immunohistochemistry. Notch expression
was semiquantitatively evaluated separately for
membranous/cytoplasmic and for nuclear staining. In
addition, we examined Her2 expression (EGFR2,
Her2/neu, ErbB2, CD340) because of its functional link
to Notch signaling.
All samples were negative for Notch3.
Membranous/cytoplasmic expression of Notch1
(p<0.0001) and Notch4 (p=0.046) was significantly
higher, whereas Notch2 expression was significantly
lower (p<0.0001) in nCP compared to CPT. Nuclear
expression of Notch1, -2 and -4 was significantly higher
in CPT compared to nCP (p<0.0001 each). Expression of
Notch2 and Notch4 showed a shift from a prevailing
membranous/cytoplasmic expression in nCP to a
predominant nuclear expression in CPT. Her2 was
weakly expressed in 42/84 CPT but only in 2/53 nCP
(p=0.0001) and positively correlated with nuclear
expression of Notch1, -2 and 4 in CPT.
In summary, a shift between membranous/cytoplasmic
(non-canonical signaling pathway) and nuclear
expression (canonical signaling pathway) of Notch1, -2
and -4 and upregulation of Her2 indicate neoplastic
transformation in human CP and may reveal new
therapeutic approaches.2013-01-01T00:00:00ZMorphological spectrum and clinical features of myopathies with tubular aggregates
http://hdl.handle.net/10201/59662
Título: Morphological spectrum and clinical features of myopathies with tubular aggregates
Autor/es principal/es: Funk, Fabian; Ceuterick-de Groote, Chantal; Martin, Jean-Jacques; Meinhardt, Axel; Taratuto, Ana L.; De Bleecker, Jan; Coster, Rudy Van; De Paepe, Boel; Schara, Ulrike; Vorgerd, Matthias; Häusler, Martin; Koppi, Stefan; Maschke, Matthias; De Jonghe, Peter; Maldergem, Lionel Van; Noel, Stéphane; Zimmermann, Christoph W.; Wirth, Stefan; Isenmann, Stefan; Stadler, Rudolf; Schröder, J. Michael; Schulz, Jörg B.; Weis, Joachim; Claeys, Kristl G.
Resumen: Tubular aggregates (TAs) are aggregates of
densely packed tubules in human skeletal muscle fibers
with particular histochemical and ultrastructural features
that most probably arise from the sarcoplasmic
reticulum. Some studies have shown an additional
mitochondrial origin of TAs. We studied the
histopathological spectrum and clinical features in a
large cohort of patients with TAs in their muscle biopsy
(106 biopsies), derived from our muscle biopsy archive
(15,412 biopsies in total). In particular, we examined
light microscopic, enzyme histochemical, immunohistochemical
and ultrastructural features in the muscle
biopsies, as well as the patients’ clinical data. We found
TAs in 0.5% of all muscle biopsies. Based on the size of
TAs, we identified two sub-groups: (1) myopathies with
large TAs (29 biopsies) in type 2 fibers and sometimes
also in type 1 fibers, absence of any other associated
disorder, and a familial history in half of the cases, and
(2) myopathies with small TAs (77 biopsies), exclusively in type 2 fibers, presence of another associated disease in
the majority of patients and mostly no familial history. In
the sub-group with large TAs, we observed a high
variability of ultrastructural changes. The most frequent
clinical symptom in both groups was limb muscle
weakness. No significant differences in clinical
presentation, age at onset or disease duration at the time
of biopsy were found between the two groups. In
conclusion, myopathies with TAs can be sub-divided
into a group with large TAs, probably corresponding to
the so-called primary TA myopathies, and into a group
with small TAs as a feature of another underlying
condition.2013-01-01T00:00:00Z