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71.
Pretreatment of tissues with potassium channel openers (KCO’s) has been observed to be cytoprotective in a broad variety of insults. This phenomenon has been proposed to be intimately linked to activation of mitochondrial potassium channels which apparently modulate the mitochondrial production of reactive oxygen species (ROS). This critical review summarizes literature findings about the mitochondrial production of ROS, the action of KCO’s on mitochondrial ROS production and the putative link to the cytoprotective action of these drugs. 相似文献
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Febrer M Goicoechea JL Wright J McKenzie N Song X Lin J Collura K Wissotski M Yu Y Ammiraju JS Wolny E Idziak D Betekhtin A Kudrna D Hasterok R Wing RA Bevan MW 《PloS one》2010,5(10):e13461
The pooid subfamily of grasses includes some of the most important crop, forage and turf species, such as wheat, barley and Lolium. Developing genomic resources, such as whole-genome physical maps, for analysing the large and complex genomes of these crops and for facilitating biological research in grasses is an important goal in plant biology. We describe a bacterial artificial chromosome (BAC)-based physical map of the wild pooid grass Brachypodium distachyon and integrate this with whole genome shotgun sequence (WGS) assemblies using BAC end sequences (BES). The resulting physical map contains 26 contigs spanning the 272 Mb genome. BES from the physical map were also used to integrate a genetic map. This provides an independent validation and confirmation of the published WGS assembly. Mapped BACs were used in Fluorescence In Situ Hybridisation (FISH) experiments to align the integrated physical map and sequence assemblies to chromosomes with high resolution. The physical, genetic and cytogenetic maps, integrated with whole genome shotgun sequence assemblies, enhance the accuracy and durability of this important genome sequence and will directly facilitate gene isolation. 相似文献
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Bonifaci N Górski B Masojć B Wokołorczyk D Jakubowska A Dębniak T Berenguer A Serra Musach J Brunet J Dopazo J Narod SA Lubiński J Lázaro C Cybulski C Pujana MA 《PloS one》2010,5(11):e14078
Recent genome-wide association studies (GWASs) have identified candidate genes contributing to cancer risk through low-penetrance mutations. Many of these genes were unexpected and, intriguingly, included well-known players in carcinogenesis at the somatic level. To assess the hypothesis of a germline-somatic link in carcinogenesis, we evaluated the distribution of somatic gene labels within the ordered results of a breast cancer risk GWAS. This analysis suggested frequent influence on risk of genetic variation in loci encoding for “driver kinases” (i.e., kinases encoded by genes that showed higher somatic mutation rates than expected by chance and, therefore, whose deregulation may contribute to cancer development and/or progression). Assessment of these predictions using a population-based case-control study in Poland replicated the association for rs3732568 in EPHB1 (odds ratio (OR) = 0.79; 95% confidence interval (CI): 0.63–0.98; Ptrend = 0.031). Analyses by early age at diagnosis and by estrogen receptor α (ERα) tumor status indicated potential associations for rs6852678 in CDKL2 (OR = 0.32, 95% CI: 0.10–1.00; Precessive = 0.044) and rs10878640 in DYRK2 (OR = 2.39, 95% CI: 1.32–4.30; Pdominant = 0.003), and for rs12765929, rs9836340, rs4707795 in BMPR1A, EPHA3 and EPHA7, respectively (ERα tumor status Pinteraction<0.05). The identification of three novel candidates as EPH receptor genes might indicate a link between perturbed compartmentalization of early neoplastic lesions and breast cancer risk and progression. Together, these data may lay the foundations for replication in additional populations and could potentially increase our knowledge of the underlying molecular mechanisms of breast carcinogenesis. 相似文献
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Rho kinase, myosin-II, and p42/44 MAPK control extracellular matrix-mediated apical bile canalicular lumen morphogenesis in HepG2 cells
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Herrema H Czajkowska D Théard D van der Wouden JM Kalicharan D Zolghadr B Hoekstra D van Ijzendoorn SC 《Molecular biology of the cell》2006,17(7):3291-3303
The molecular mechanisms that regulate multicellular architecture and the development of extended apical bile canalicular lumens in hepatocytes are poorly understood. Here, we show that hepatic HepG2 cells cultured on glass coverslips first develop intercellular apical lumens typically formed by a pair of cells. Prolonged cell culture results in extensive organizational changes, including cell clustering, multilayering, and apical lumen morphogenesis. The latter includes the development of large acinar structures and subsequent elongated canalicular lumens that span multiple cells. These morphological changes closely resemble the early organizational pattern during development, regeneration, and neoplasia of the liver and are rapidly induced when cells are cultured on predeposited extracellular matrix (ECM). Inhibition of Rho kinase or its target myosin-II ATPase in cells cultured on glass coverslips mimics the morphogenic response to ECM. Consistently, stimulation of Rho kinase and subsequent myosin-II ATPase activity by lipoxygenase-controlled eicosatetranoic acid metabolism inhibits ECM-mediated cell multilayering and apical lumen morphogenesis but not initial apical lumen formation. Furthermore, apical lumen remodeling but not cell multilayering requires basal p42/44 MAPK activity. Together, the data suggest a role for hepatocyte-derived ECM in the spatial organization of hepatocytes and apical lumen morphogenesis and identify Rho kinase, myosin-II, and MAPK as potentially important players in different aspects of bile canalicular lumen morphogenesis. 相似文献
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Rapid induction of distinct stress responses after the release of singlet oxygen in Arabidopsis 总被引:15,自引:0,他引:15
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op den Camp RG Przybyla D Ochsenbein C Laloi C Kim C Danon A Wagner D Hideg E Göbel C Feussner I Nater M Apel K 《The Plant cell》2003,15(10):2320-2332
The conditional fluorescent (flu) mutant of Arabidopsis accumulates the photosensitizer protochlorophyllide in the dark. After a dark-to-light shift, the generation of singlet oxygen, a nonradical reactive oxygen species, starts within the first minute of illumination and was shown to be confined to plastids. Immediately after the shift, plants stopped growing and developed necrotic lesions. These early stress responses of the flu mutant do not seem to result merely from physicochemical damage. Peroxidation of chloroplast membrane lipids in these plants started rapidly and led to the transient and selective accumulation of a stereospecific and regiospecific isomer of hydroxyoctadecatrieonic acid, free (13S)-HOTE, that could be attributed almost exclusively to the enzymatic oxidation of linolenic acid. Within the first 15 min of reillumination, distinct sets of genes were activated that were different from those induced by superoxide/hydrogen peroxide. Collectively, these results demonstrate that singlet oxygen does not act primarily as a toxin but rather as a signal that activates several stress-response pathways. Its biological activity in Arabidopsis exhibits a high degree of specificity that seems to be derived from the chemical identity of this reactive oxygen species and/or the intracellular location at which it is generated. 相似文献
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Dominika Drulis-Fajdasz Adam Krzystyniak Alicja Puścian Agata Pytyś Kinga Gostomska-Pampuch Natalia Pudełko-Malik Jerzy Ł. Wiśniewski Piotr Młynarz Arkadiusz Miazek Tomasz Wójtowicz Jakub Włodarczyk Kamila Duś-Szachniewicz Agnieszka Gizak Jacek R. Wiśniewski Dariusz Rakus 《Aging cell》2023,22(9):e13928
Inhibition of glycogen breakdown blocks memory formation in young animals, but it stimulates the maintenance of the long-term potentiation, a cellular mechanism of memory formation, in hippocampal slices of old animals. Here, we report that a 2-week treatment with glycogen phosphorylase inhibitor BAY U6751 alleviated memory deficits and stimulated neuroplasticity in old mice. Using the 2-Novel Object Recognition and Novel Object Location tests, we discovered that the prolonged intraperitoneal administration of BAY U6751 improved memory formation in old mice. This was accompanied by changes in morphology of dendritic spines in hippocampal neurons, and by “rejuvenation” of hippocampal proteome. In contrast, in young animals, inhibition of glycogen degradation impaired memory formation; however, as in old mice, it did not alter significantly the morphology and density of cortical dendritic spines. Our findings provide evidence that prolonged inhibition of glycogen phosphorolysis improves memory formation of old animals. This could lead to the development of new strategies for treatment of age-related memory deficits. 相似文献
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Lewandowska D Simpson CG Clark GP Jennings NS Barciszewska-Pacak M Lin CF Makalowski W Brown JW Jarmolowski A 《The Plant cell》2004,16(5):1340-1352
Factors affecting splicing of plant U12-dependent introns have been examined by extensive mutational analyses in an in vivo tobacco (Nicotiana tabacum) protoplast system using introns from three different Arabidopsis thaliana genes: CBP20, GSH2, and LD. The results provide evidence that splicing efficiency of plant U12 introns depends on a combination of factors, including UA content, exon bridging interactions between the U12 intron and flanking U2-dependent introns, and exon splicing enhancer sequences (ESEs). Unexpectedly, all three plant U12 introns required an adenosine at the upstream purine position in the branchpoint consensus UCCUURAUY. The exon upstream of the LD U12 intron is a major determinant of its higher level of splicing efficiency and potentially contains two ESE regions. These results suggest that in plants, U12 introns represent a level at which expression of their host genes can be regulated. 相似文献
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Chromosomal imbalance in gametes and embryos is one of the factors contributing to early embryonic mortality. Although the rate of chromosomally abnormal sperm cells is low and usually does not exceed 1%, there is no clear indication of fertilizing potential of such gametes. The aim of the experiment was to investigate the type and incidence of numerical chromosomal aberrations in spermatozoa produced by fertile boars used in artificial insemination (AI). We used the protocol of fluorescent in situ hybridization (FISH) on sperm interphase nuclei with molecular probes for porcine chromosome pairs 1 and 10. Altogether 12?348 sperm cells were examined. Disomy was observed in spermatozoa of all seven AI boars whereas only one diploid cell was identified in all screened sperm cells. The average rate of chromosomally unbalanced sperm was 0.105% (13/12 348) with an inter-individual variation from 0.048% to 0.194%. Among abnormal sperm cells, both disomy (0.097%) and diploidy (0.008%) were detected. Nullisomy was not included into calculations. The estimated aneuploidy rate calculated by doubling the number of disomic cells was 0.194%. Chromosome pair 10 was significantly more often involved in non-disjunction (75%, 9/12 aneuploid sperm cells) than chromosome pair 1 (25%, 3/12). We have shown for the pig that the rate of disomic cells falls into a range presented by other authors, whereas that of diploid spermatozoa appeared to be lower in the present study. In conclusion, numerical chromosome aberrations were present in spermatozoa of all AI boars analyzed in this study. Therefore, it can be assumed that the presence of unbalanced spermatozoa at the level observed in fertile males does not significantly affect their reproductive potential. 相似文献