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Transmission electron micrographs of a cardiac muscle (A) and skeletal muscle cells (B) from the control group. Characteristic central and peripheral positions of the nuclelus and a typical distribution of nucleolar components (inset) was observed Nuclei (N), Nucleolus (n), nucleolar organisation region (white arrow head) and the granular component (black arrow head). Myofibrils (MF), mitochondria (m) and the perinuclear chromatin (C) were also revealed. Scale bars:
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In the present study, we compared the cell damage response in skeletal and cardiac muscle tissue when exposed to doxorubicin. This was carried out by means of a less invasive informative substitute to endomyocardiac biopsy based on Hsp70 immunodetection and a subcellular analysis of the nucleolus. Male Sprague Dawley rats (62 g body weight) were ra...
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Context 1
... concentric accumulation of macromolecules in random distribution, typical of a cell under normal conditions, was observed in the nucleolus of both muscle types from the CON group, where a region of nucleolar organisation (RNO) and a dense fibril and granular component (DFC and GC, respectively; Fig. 1) were identified. In contrast, in the DOX-I and DOX-II groups, a tendency towards segregation of components or compact nucleolar structures was observed for all DOX post- treatment times (Figs. 2, 3). In the nucleoli of cardiac tissue (A-D, Figs. 1, 2) and skeletal muscle tissue (E-H, Figs. 1, 2), the segregation was characterised ...
Context 2
... of nucleolar organisation (RNO) and a dense fibril and granular component (DFC and GC, respectively; Fig. 1) were identified. In contrast, in the DOX-I and DOX-II groups, a tendency towards segregation of components or compact nucleolar structures was observed for all DOX post- treatment times (Figs. 2, 3). In the nucleoli of cardiac tissue (A-D, Figs. 1, 2) and skeletal muscle tissue (E-H, Figs. 1, 2), the segregation was characterised principally by a ring- like configuration, with a less electron-dense element in a central or lateral location (Fig. 2, A-D, E, H; Fig. 3, A-D, F). The compact nucleolar structures evidenced a tight grouping of electron-dense elements in a spherical shape, ...
Context 3
... and granular component (DFC and GC, respectively; Fig. 1) were identified. In contrast, in the DOX-I and DOX-II groups, a tendency towards segregation of components or compact nucleolar structures was observed for all DOX post- treatment times (Figs. 2, 3). In the nucleoli of cardiac tissue (A-D, Figs. 1, 2) and skeletal muscle tissue (E-H, Figs. 1, 2), the segregation was characterised principally by a ring- like configuration, with a less electron-dense element in a central or lateral location (Fig. 2, A-D, E, H; Fig. 3, A-D, F). The compact nucleolar structures evidenced a tight grouping of electron-dense elements in a spherical shape, in which an accumulation of less ...
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Breast cancer is the most common malignancy in women worldwide. While doxorubicin is part of the standard therapy for metastatic breast cancer, it has limited success. Pitavastatin, has been shown to enhance the anti-cancer activity of certain therapeutics. The current study therefore explored the anti-cancer activity of the combined treatment of d...
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... f Immunogold electron microscopy illustrating an IGC (asterisk) decorated with gold particles of TMG-cap immunoreactivity. Scale bars: c, d 1 µm; e 700 nm; f 250 nm myofibers and other cell types by nucleolar stress-induced drugs, such as actinomycin D and doxorubicin, which interfere with nucleolar transcription (Puvion-Dutilleul et al. 1992;Maita et al. 2009). Interestingly, nucleolar alterations have also been associated with reduced SMN levels in the MNs from a mouse model of type I SMA, suggesting an SMN-dependent perturbation of nucleolar functions . ...
Type I spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by the loss or mutation of the survival motor neuron 1 (SMN1) gene. The reduction in SMN protein levels in SMA leads to the degeneration of motor neurons and muscular atrophy. In this study, we analyzed the nuclear reorganization in human skeletal myofibers from a type I SMA patient carrying a deletion of exons 7 and 8 in the SMN1 gene and two SMN2 gene copies and showing reduced SMN protein levels in the muscle compared with those in control samples. The morphometric analysis of myofiber size revealed the coexistence of atrophic and hypertrophic myofibers in SMA samples. Compared with controls, both nuclear size and the nuclear shape factor were significantly reduced in SMA myonuclei. Nuclear reorganization in SMA myonuclei was characterized by extensive heterochromatinization, the aggregation of splicing factors in large interchromatin granule clusters, and nucleolar alterations with the accumulation of the granular component and a loss of fibrillar center/dense fibrillar component units. These nuclear alterations reflect a severe perturbation of global pre-mRNA transcription and splicing, as well as nucleolar dysfunction, in SMA myofibers. Moreover, the finding of similar nuclear reorganization in both atrophic and hypetrophic myofibers provides additional support that the SMN deficiency in SMA patients may primarily affect the skeletal myofibers.
