Protein-synthesis inhibition induces perichromatin granule accumulation and intranuclear rodlet formation in osmotically stimulated supraoptic neurons

Lafarga, Miguel; Berciano, Marı́a T.; Andrés, M. A.

doi:10.1007/bf00185894

Cited by 24 publications

(13 citation statements)

References 34 publications

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“…Malatesta et al 1998); weaker labelling for RNA polymerase II and SC-35, and higher amounts of condensed chromatin indicate reduced transcriptional activity; higher densities of PG, site of intranuclear storage and transport of already spliced (pre)-mRNA (Fakan 2004), suggest altered pre-mRNA processing and/or impaired intranuclear or nucleus-cytoplasmic transport (e.g. Lafarga et al 1993).…”

Section: Discussionmentioning

confidence: 98%

A long-term study on female mice fed on a genetically modified soybean: effects on liver ageing

Malatesta

Boraldi

Annovi

et al. 2008

Histochem Cell Biol

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Liver represents a suitable model for monitoring the effects of a diet, due to its key role in controlling the whole metabolism. Although no direct evidence has been reported so far that genetically modified (GM) food may affect health, previous studies on hepatocytes from young female mice fed on GM soybean demonstrated nuclear modifications involving transcription and splicing pathways. In this study, the effects of this diet were studied on liver of old female mice in order to elucidate possible interference with ageing. The morpho-functional characteristics of the liver of 24-month-old mice, fed from weaning on control or GM soybean, were investigated by combining a proteomic approach with ultrastructural, morphometrical and immunoelectron microscopical analyses. Several proteins belonging to hepatocyte metabolism, stress response, calcium signalling and mitochondria were differentially expressed in GM-fed mice, indicating a more marked expression of senescence markers in comparison to controls. Moreover, hepatocytes of GM-fed mice showed mitochondrial and nuclear modifications indicative of reduced metabolic rate. This study demonstrates that GM soybean intake can influence some liver features during ageing and, although the mechanisms remain unknown, underlines the importance to investigate the long-term consequences of GM-diets and the potential synergistic effects with ageing, xenobiotics and/or stress conditions.

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Section: Discussionmentioning

confidence: 98%

A long-term study on female mice fed on a genetically modified soybean: effects on liver ageing

Malatesta

Boraldi

Annovi

et al. 2008

Histochem Cell Biol

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“…The occurrence of both rodlets and crystalloids composed of bundles of fibrils has been reported in the nuclei of certain neuronal types, but not in normal EGL cells (for a review, see Peters et al 1991). However, experimental evidence indicates that alterations of transcription by actinomycin D (Scheer et al 1984) or cycloheximide treatments (Lafarga et al 1993) and heat-shock (Welch and Suhan 1985) induce nuclear polymerization of cytoskeletal proteins resulting in bundles of filaments in cells that usually lack these structures. Our results extend the formation of intranuclear rodlets to a neuronal model of apoptosis and are consistent with the expression of these structures in response to arrested cellular transcription associated with chromatin degradation.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis induced by methylazoxymethanol in developing rat cerebellum: organization of the cell nucleus and its relationship to DNA and rRNA degradation

Lafarga

Lerga

Andrés

et al. 1997

Cell and Tissue Research

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We present a cytological and biochemical study of the cell death of granule cell precursors in developing rat cerebellum following treatment with the cytotoxic agent methylazoxymethanol (MAM) during the first postnatal week. The density of apoptotic figures per square millimeter progressively increases after 6, 12, 24 and 44 h of treatment, whereas cells immunoreactive for proliferating cell nuclear antigen tend to disappear in the external granular layer (EGL). DNA migration on gel electrophoresis reveals a typical ladder pattern of internucleosomal cleavage following MAM treatment, whereas gel electrophoresis of rRNA shows a conspicuous degradation of both 28S and 18S rRNAs. Ultrastructural analysis has revealed the alterations of structures containing chromatin and ribonucleoprotein (RNP) in dying cells of the EGL. The typical granular beaded configuration of the condensed chromatin changes to a denser, more homogeneous texture suggesting nucleosomal disruption. The reorganization of RNP nuclear domains is reflected by the appearance of dispersed nucleoplasmic RNP particles and the formation of a coiled-body-like structure. However, typical nuclear domains involved in the splicing of RNAs, namely interchromatin granule clusters and typical "coiled bodies", are not found in apoptotic cells. Intranuclear bundles of filaments have also been detected. In the cytoplasm, the presence of dispersed single ribosomes is an initial sign of apoptosis. The massive dispersion and disruption of ribosomes detected after 24 h and 44 h of MAM treatment is reflected by the degradation of both 28S and 18s rRNAs. These results show that MAM treatment provides a useful experimental model for the study of apoptosis in the developing central nervous system. The organization of the cell nucleus in cells undergoing apoptosis clearly reflects a disruption of the nuclear compartments involved in transcription and the processing and transport of RNA and is related to the patterns of DNA and rRNA degradation.

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“…In fact, PG represent storage and/or transport sites for spliced mRNA, and PG accumulation has been described as a consequence of altered pre-mRNA processing as well as of impaired intranuclear or nucleus-to-cytoplasm transport (e.g. Puvion et al, 1977;Puvion-Dutilleul et al, 1981;Lafarga et al, 1993;Zancanaro et al, 1993). Accordingly, a decrease in nucleus-to-cytoplasm transport factors (Pujol et al, 2002) has been reported during ageing, when the degradation systems also undergo alterations (Jameson, 2004) leading to the accumulation of crosslinked, insoluble and often oxidized proteins which may damage the intracellular transport mechanisms (Hallen, 2002;Kim et al, 2001); the intranuclear accumulation of RNA with poly(A) tails, known to be involved in stabilization, localization and translation of mRNAs (e.g.…”

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confidence: 99%

Nuclei of aged myofibres undergo structural and functional changes suggesting impairment in RNA processing

Malatesta¹,

Perdoni²,

Muller³

et al. 2009

Eur J Histochem

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Advancing adult age is associated with a progressive decrease in skeletal muscle mass, strength and quality known as sarcopenia. The mechanisms underlying age-related skeletal muscle wasting and weakness are manifold and still remain to be fully elucidated. Despite the increasing evidence that the progress of muscle diseases leading to muscle atrophy/dystrophy may be related to defective RNA processing, no data on the morpho-functional features of skeletal muscle nuclei in sarcopenia are available at present. In this view, we have investigated, by combining morphometry and immunocytochemistry at light and electron microscopy, the fine structure of myonuclei as well as the distribution and amount of RNA processing factors in skeletal myofibres of biceps brachii and quadriceps femoris from adult and old rats. Results demonstrate that the myonuclei of aged type II fibres show an increased amount of condensed chromatin and lower amounts of phosphorylated polymerase II and DNA/RNA hybrid molecules, clearly indicating a decrease in pre-mRNA transcription rate compared to adult animals. In addition, myonuclei of aged fibres show decreased amounts of nucleoplasmic splicing factors and an accumulation of cleavage factors, polyadenilated RNA and perichromatin granules, suggesting a reduction in the processing and transport rate of premRNA. During ageing, it seems therefore that in rat myonuclei the entire production chain of mRNA, from synthesis to cytoplasmic export, is less efficient. This failure likely contributes to the reduced responsiveness of muscle cells to anabolic stimuli in the elderly.

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Protein-synthesis inhibition induces perichromatin granule accumulation and intranuclear rodlet formation in osmotically stimulated supraoptic neurons

Cited by 24 publications

References 34 publications

A long-term study on female mice fed on a genetically modified soybean: effects on liver ageing

A long-term study on female mice fed on a genetically modified soybean: effects on liver ageing

Apoptosis induced by methylazoxymethanol in developing rat cerebellum: organization of the cell nucleus and its relationship to DNA and rRNA degradation

Nuclei of aged myofibres undergo structural and functional changes suggesting impairment in RNA processing

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