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21.
Angelos Papaspyropoulos Orsalia Hazapis Abdullah Altulea Aikaterini Polyzou Panayotis Verginis Konstantinos Evangelou Maria Fousteri Argyris Papantonis Marco Demaria Vassilis Gorgoulis 《Aging cell》2023,22(9):e13893
Cellular senescence constitutes a generally irreversible proliferation barrier, accompanied by macromolecular damage and metabolic rewiring. Several senescence types have been identified based on the initiating stimulus, such as replicative (RS), stress-induced (SIS) and oncogene-induced senescence (OIS). These senescence subtypes are heterogeneous and often develop subset-specific phenotypes. Reduced protein synthesis is considered a senescence hallmark, but whether this trait pertains to various senescence subtypes and if distinct molecular mechanisms are involved remain largely unknown. Here, we analyze large published or experimentally produced RNA-seq and Ribo-seq datasets to determine whether major translation-regulating entities such as ribosome stalling, the presence of uORFs/dORFs and IRES elements may differentially contribute to translation deficiency in senescence subsets. We show that translation-regulating mechanisms may not be directly relevant to RS, however uORFs are significantly enriched in SIS. Interestingly, ribosome stalling, uORF/dORF patterns and IRES elements comprise predominant mechanisms upon OIS, strongly correlating with Notch pathway activation. Our study provides for the first time evidence that major translation dysregulation mechanisms/patterns occur during cellular senescence, but at different rates depending on the stimulus type. The degree at which those mechanisms accumulate directly correlates with translation deficiency levels. Our thorough analysis contributes to elucidating crucial and so far unknown differences in the translation machinery between senescence subsets. 相似文献
22.
Electrocardiographic alterations induced by zinc ions on isolated guinea pig heart preparations 总被引:2,自引:0,他引:2
On guinea pig isolated hearts perfused according to the Langendorff technique, by Chenoweth's solution, and by various concentration
of ZnCl2, surface E.C.G. was recorded for 65 min, after the equilibration period.
Concentrations of zinc corresponding to plasma free and exchangable fractions (1.5 μM) exerted only a nonstatistically significant sinus bradycardia. Bradycardia was prominent between the 25th and 35th min of
perfusion, with higher concentrations of zinc (7.5 and 15 μM). In even higher (toxic) concentrations of zinc (30 μM), various types of arrhythmias were recorded, such as first degree AV block, idioventricular rhythms, atrial, and ventricular
extrasystoles, and asystolia, evoked since the 15th min of perfusion.
The above-mentioned findings in relation to low plasma zinc concentrations found in coronary patients and experimental myocardial
infarction as well as myocardial injury related to metal fume fever, brought our attention to the involvement of this divalent
cation to cardiac physiology and pathophysiology. 相似文献
23.
Relationships between Cadmium, Zinc, Cd-Peptide, and Organic Acid in Tobacco Suspension Cells 总被引:11,自引:4,他引:7
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Responses of tobacco (Nicotiana tabacum) suspension cells to Cd and Zn were studied in the presence and absence of ligand of Cd-peptide in order to understand the role of this peptide versus other mechanisms in Cd and Zn accumulation and accommodation in plants. With 45 micromolar Cd and 300 micromolar Zn (non-growth-inhibiting levels), metals appeared rapidly within cells, and intracellular Cd and Zn reached medium concentrations after 6 to 10 hours. Cd-peptide was observed in response to Cd after 2 hours, but this form only accounted for ~30% of soluble Cd after 24 hours. Peptide was not observed in cells exposed to 300 micromolar Zn for up to 7 days. Organic acid-to-metal stoichiometry indicated that endogenous organic acid content of cells was more than sufficient to complex absorbed metals and no evidence was found for stimulation of organic acid biosynthesis by Cd or Zn. Metal-complexing potential of organic acids for Cd and Zn versus endogenous cations is discussed as is vacuolar-extravacuolar distribution of metals. The absence of Cd-peptide does not limit Cd-accumulation in the system studied. Results suggest that tobacco suspension cells accommodate the presence of non-growth-inhibiting and growth-inhibiting levels of Cd and Zn by sequestration in the vacuole as complexes with endogenous organic acids and that this may be a principal means for accommodation of Cd as well as Zn in the presence and absence of Cd-peptide. 相似文献
24.
Alexandra Evangelou Christos Zikos Evangelia Livaniou Gregory P Evangelatos 《Journal of peptide science》2004,10(10):631-635
Humanin is a novel, 24-mer residue bioactive peptide, which antagonizes Alzheimer's disease (AD) related neurotoxicity and offers a hope for developing new therapeutics against AD. Access to adequate amounts of pure humanin is a prerequisite for further, thorough, investigation of the pharmacological properties and therapeutic potency of the peptide. Until now, humanin has been obtained mainly by molecular biology techniques. In this work the Fmoc solid-phase synthesis of humanin on an in-house prepared 2-Cl-tritylamidomethyl polystyrene resin is described fully. Special precautions, i.e. prolonged deprotection steps, should be taken to achieve a high overall yield, since humanin seems to contain a 'difficult sequence' (R4G5F6S7C8L9) near its highly lipophilic, biologically important region L9L10L11L12. 相似文献
25.
A D Tselepis A Evangelou D Tsoukatos C A Demopoulos V M Kapoulas 《Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol.》1987,87(1):41-46
AGEPC administration into Wistar rats caused no remarkable thrombocytopenia, slight decrease of the percent count of PMNs in whole blood accompanied by anequal leukocytopenia and a transient increase in hematocrit, due to fluid extraversion. Apart from the dramatic fall in blood pressure caused by AGEPC, relatively sinus bradycardia was recorded at doses over 6 micrograms/kg b.w. S-T segment elevation, mainly evident in II, III and AVF leads, was also recorded within the first minutes after AGEPC administration, at doses over 1 microgram/kg b.w. At lethal doses, various degrees of A-V block resulting in complete A-V block with idioventricular rhythm, or injury pattern resulting in ventricular fibrillation or ventricular flutter, were recorded. At sublethal doses no arrhythic manifestations were recorded, while S-T segment elevation upward inversion became gradually normal. 相似文献
26.
Evangelou AI Winter SF Huss WJ Bok RA Greenberg NM 《Journal of cellular biochemistry》2004,91(4):671-683
The growth, development, and differentiation of the prostate gland is largely dependent on the action of androgens and peptide growth factors that act differentially at the level of the mesenchymal and epithelial compartments. It is our premise that to understand the emergence of metastatic and hormone refractory prostate cancer we need to investigate: (1) how androgen action at the level of the mesenchyme induces the production of peptide growth factors that in turn can facilitate the growth and development of the epithelial compartment; (2) how androgen action at the level of the epithelium induces and maintains cellular differentiation, function, and replicative senescence; and (3) how transformation of the prostate gland can corrupt androgen and growth factor signaling homeostasis. To this end, we focus our discussion on how deregulation of the growth factor signaling axis can cooperate with deregulation of the androgen signaling axis to facilitate transformation, metastasis, and the emergence of the hormone refractory and neuroendocrine phenotypes associated with progressive androgen-independent prostate cancer. Finally, we suggest a working hypothesis to explain why hormone ablation therapy works to control early disease but fails to control, and may even facilitate, advanced prostate cancer. 相似文献
27.
Vicky P. Kalfakakou Angelos M. Evangelou Jacques Benveniste Bernard Arnoux 《Biological trace element research》1993,38(3):289-299
Isolated guinea pig hearts were perfused, by the Langendorff technique, with 30, 15, 7.5, and 1.5 μM Zn2+ in Chenoweth solution. Contractile force, coronary flow, and heart rate were recorded by means of Narco IV Physiograph. Calcium
inhibitor (Verapamil 1 μM) and anion inhibitor (DIDS: 0.1, 1, and 5 μM) were used subsequently in the perfusing solutions in order to distinguish some of the possible mechanisms that Zn2+ uses to exert its action on cardiac myocytes. Isomolar to zinc concentration of Pb (II) and Co (II) were used to elucidate
whether zinc effects on heart are specific for this metal. All hearts were used to estimate their zinc and calcium content
by means of AAS (Atomic Absorption Spectrometry).
Our findings suggest that the higher the Zn2+ concentration, the more toxic effects on heart are expressed by rapid reversible contractile force reduction and reversible
specific changes of heart rate and flow. Zinc 1.5 μM in the perfusing solution benefits heart performance, but not significantly. Furthermore, the metal exerts specific effects
on guinea pig heart, and it is rather possible that these effects on cardiac myocytes are held through cell membrane receptors. 相似文献
28.
Solution structure of Ser14Gly-humanin, a potent rescue factor against neuronal cell death in Alzheimer's disease 总被引:2,自引:0,他引:2
Benaki D Zikos C Evangelou A Livaniou E Vlassi M Mikros E Pelecanou M 《Biochemical and biophysical research communications》2006,349(2):634-642
The NMR solution study of Ser14Gly-humanin (S14G-HN), a 1000-fold more potent derivative of humanin (HN), is reported. HN is 24-residue peptide that selectively suppresses neuronal cell death caused by Alzheimer's disease (AD)-specific insults and offers hope for the development of a cure against AD. In aqueous solution the NMR data show that S14G-HN is a flexible peptide with turn-like structures in its conformational ensemble distributed over an extensive part of its sequence from Pro3 to Glu15. In the more lipophilic environment of 30% TFE, an alpha-helical structure spanning residues Phe6 to Thr13 is identified. Comparison of these findings to the NMR structure of the parent HN and to existing structure-function relationship literature data outlines the important for activity structural features for this class of neuroprotective peptides, and brings forth flexibility as an important characteristic that may facilitate interactions with functional counterparts of the neuroprotection pathway. 相似文献
29.
Background
Influential medical journals shape medical science and practice and their prestige is usually appraised by citation impact metrics, such as the journal impact factor. However, how permanent are medical journals and how stable is their impact over time?Methods and Results
We evaluated what happened to general medical journals that were publishing papers half a century ago, in 1959. Data were retrieved from ISI Web of Science for citations and PubMed (Journals function) for journal history. Of 27 eligible journals publishing in 1959, 4 have stopped circulation (including two of the most prestigious journals in 1959) and another 7 changed name between 1959 and 2009. Only 6 of these 27 journals have been published continuously with their initial name since they started circulation. The citation impact of papers published in 1959 gives a very different picture from the current journal impact factor; the correlation between the two is non-significant and very close to zero. Only 13 of the 5,223 papers published in 1959 received at least 5 citations in 2009.Conclusions
Journals are more permanent entities than single papers, but they are also subject to major change and their relative prominence can change markedly over time. 相似文献30.
Irene Stefanaki Orestis A. Panagiotou Elisavet Kodela Helen Gogas Katerina P. Kypreou Foteini Chatzinasiou Vasiliki Nikolaou Michaela Plaka Iro Kalfa Christina Antoniou John P. A. Ioannidis Evangelos Evangelou Alexander J. Stratigos 《PloS one》2013,8(2)