Ultrastructural changes in nucleoli and fibrillar centers under the effect of local ultraviolet microbeam irradiation of interphase culture cells

Зацепина, О. В.; Voronkova, L.N.; Sakharov, V. N.; Chentsov, Yu. S.

doi:10.1016/0014-4827(89)90185-7

Cited by 17 publications

(12 citation statements)

References 15 publications

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“…Subnuclear localization of p53 and another nucleolar protein, nucleophosmin, were examined by immunofluorescence using their respective antibodies. Note that after actinomycin D treatment nucleophosmin localized mainly to the nucleoplasm indicating partial disruption of nucleolar structure as described previously (Zatsepina et al, 1989;Chan et al, 1996;Haaf and Ward, 1996).…”

Section: Atp-dependent P53 Nucleolar Localization O Karni-schmidt Et Alsupporting

confidence: 78%

Energy-dependent nucleolar localization of p53 in vitro requires two discrete regions within the p53 carboxyl terminus

et al. 2007

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The p53 tumor suppressor is a nucleocytoplasmic shuttling protein that is found predominantly in the nucleus of cells. In addition to mutation, abnormal p53 cellular localization is one of the mechanisms that inactivate p53 function. To further understand features of p53 that contribute to the regulation of its trafficking within the cell, we analysed the subnuclear localization of wild-type and mutant p53 in human cells that were either permeabilized with detergent or treated with the proteasome inhibitor MG132. We, here, show that either endogenously expressed or exogenously added p53 protein localizes to the nucleolus in detergent-permeabilized cells in a concentration-and ATP hydrolysis-dependent manner. Two discrete regions within the carboxyl terminus of p53 are essential for nucleolar localization in permeabilized cells. Similarly, localization of p53 to the nucleolus after proteasome inhibition in unpermeabilized cells requires sequences within the carboxyl terminus of p53. Interestingly, genotoxic stress markedly decreases the association of p53 with the nucleolus, and phosphorylation of p53 at S392, a site that is modified by such stress, partially impairs its nucleolar localization. The possible significance of these findings is discussed.

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Section: Atp-dependent P53 Nucleolar Localization O Karni-schmidt Et Alsupporting

confidence: 78%

Energy-dependent nucleolar localization of p53 in vitro requires two discrete regions within the p53 carboxyl terminus

et al. 2007

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“…When an individual nucleolus is inactivated by localized UV irradiation, the remaining intact nucleoli within the same nucleus expand such that the whole nucleolar function is not compromised (Zatsepina et al ., 1989). UV irradiation can be expected to cause nucleolar disruption in two ways: by direct blockage of rDNA transcription and by global inhibition of RNA Pol II transcription.…”

Section: Resultsmentioning

confidence: 99%

Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage and other stresses

2003

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p53 protects against cancer through its capacity to induce cell cycle arrest or apoptosis under a large variety of cellular stresses. It is not known how such diversity of signals can be integrated by a single molecule. However, the literature reveals that a common denominator in all p53-inducing stresses is nucleolar disruption. We thus postulated that the impairment of nucleolar function might stabilize p53 by preventing its degradation. Using micropore irradiation, we demonstrate that large amounts of nuclear DNA damage fail to stabilize p53 unless the nucleolus is also disrupted. Forcing nucleolar disruption by anti-upstream binding factor (UBF) microinjection (in the absence of DNA damage) also causes p53 stabilization. We propose that the nucleolus is a stress sensor responsible for maintenance of low levels of p53, which are automatically elevated as soon as nucleolar function is impaired in response to stress. Our model integrates all known p53-inducing agents and also explains cell cycle-related variations in p53 levels which correlate with established phases of nucleolar assembly/disassembly through the cell cycle.

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“…Moreover, the presence of nucleoli‐like bodies is indicative of increased protein synthesis and nucleocytoplasmic exchange (Beltran & Stuckey 1972). This nucleolar segregation probably reflects DNA binding and inhibition of DNA‐dependent RNA synthesis (Reddy & Svoboda 1968; Zatsepina et al . 1989).…”

Section: Discussionmentioning

confidence: 99%

Morphological evaluation of the radioprotective effects of melatonin against X‐ray‐induced early and acute testis damage in Albino rats: an animal model

Hussein

Abu-Dief

El-Ghait

et al. 2006

Int J Experimental Path

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Irradiation has profound effects on the reproductive function. Our knowledge about radioprotective effects of melatonin against X-ray-induced testis damage is rudimentary. In this investigation, we hypothesized that melatonin can minimize germ-cell depletion and morphological features of cell damage in testis following X-ray irradiation (XRI). To examine these effects, and to test our hypothesis, an animal model comprised of 60 Albino rats was established. The animals were divided into five groups: Group 1, non-irradiated; Group 2, X-ray irradiated (XRI, 8 Grays); Group 3, XRI pretreated with solvent (ethanol and phosphate-buffered saline); Group 4, non-irradiated group treated with melatonin and Group 5, XRI pretreated with melatonin. The testes were evaluated for both histological (light microscopy) and ultrastructural changes (transmission electron microscopy). Histologically, there were marked depletions (66%) of the germinal epithelial cells, in XRI group (Groups 2 and 3), whereas these changes were almost absent in XRI testis of animals pretreated with melatonin (Group 5). The number of spermatogenic cells in XRI testis of animals pretreated with melatonin (Group 5) was comparable (95%) to that of non-irradiated group (Groups 1 and 4) but significantly (P < 0.05) higher than those in XRI testis (34%, Groups 2 and 3). Ultrastructurally, XRI testis (Groups 2 and 3) showed features of apoptosis (condensation of the nuclei, vacuolization of the cytoplasm, increased cytoplasmic density and apoptotic bodies). These features were absent in XRI testis of animals pretreated with melatonin (Group 5). Also, this Group showed features of an increased metabolic activity (large acrosomal vesicle, prominent Golgi, increased mitotic activity, increased complement of cytoplasmic organelles and appearance of nucleoli-like bodies). There was a minimal depletion of the Sertoli and Leydig cells following XRI. Also, morphological features of apoptosis were infrequent in these cells. Administration of melatonin (MEL) prior to irradiation can protect testis against its destructive effects. The protective effects include amelioration of germ-cell depletion and apoptotic changes. The clinical ramifications of these observations mandate further studies.

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Ultrastructural changes in nucleoli and fibrillar centers under the effect of local ultraviolet microbeam irradiation of interphase culture cells

Cited by 17 publications

References 15 publications

Energy-dependent nucleolar localization of p53 in vitro requires two discrete regions within the p53 carboxyl terminus

Energy-dependent nucleolar localization of p53 in vitro requires two discrete regions within the p53 carboxyl terminus

Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage and other stresses

Morphological evaluation of the radioprotective effects of melatonin against X‐ray‐induced early and acute testis damage in Albino rats: an animal model

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