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51.
p53 Gene deficiency promotes hypoxia-induced pulmonary hypertension and vascular remodeling in mice 总被引:1,自引:0,他引:1
Mizuno S Bogaard HJ Kraskauskas D Alhussaini A Gomez-Arroyo J Voelkel NF Ishizaki T 《American journal of physiology. Lung cellular and molecular physiology》2011,300(5):L753-L761
Chronic hypoxia induces pulmonary arterial remodeling, resulting in pulmonary hypertension and right ventricular hypertrophy. Hypoxia has been implicated as a physiological stimulus for p53 induction and hypoxia-inducible factor-1α (HIF-1α). However, the subcellular interactions between hypoxic exposure and expression of p53 and HIF-1α remain unclear. To examine the role of p53 and HIF-1α expression on hypoxia-induced pulmonary arterial remodeling, wild-type (WT) and p53 knockout (p53KO) mice were exposed to either normoxia or hypoxia for 8 wk. Following chronic hypoxia, both genotypes demonstrated elevated right ventricular pressures, right ventricular hypertrophy as measured by the ratio of the right ventricle to the left ventricle plus septum weights, and vascular remodeling. However, the right ventricular systolic pressures, the ratio of the right ventricle to the left ventricle plus septum weights, and the medial wall thickness of small vessels were significantly greater in the p53KO mice than in the WT mice. The p53KO mice had lower levels of p21 and miR34a expression, and higher levels of HIF-1α, VEGF, and PDGF expression than WT mice following chronic hypoxic exposure. This was associated with a higher proliferating cell nuclear antigen expression of pulmonary artery in p53KO mice. We conclude that p53 plays a critical role in the mitigation of hypoxia-induced small pulmonary arterial remodeling. By interacting with p21 and HIF-1α, p53 may suppress hypoxic pulmonary arterial remodeling and pulmonary arterial smooth muscle cell proliferation under hypoxia. 相似文献
52.
In the Hruby Jeseník Mts of the Czech Republic, research was carried out from 2001–2005 aimed at completing an up-to-date
census of alpine juniper [Juniperus communis subsp. alpine (Smith) Čelakovsky] and an evaluation of the overall health status of the populations, and at investigating the impacts of
the main environmental factors on the viability of this species. 13 sites were identified with 283 individuals in total, but
the sites differed dramatically in the number of recorded individuals. Comparisons with historical literature sources show
that the species has been in decline. The main reasons for this decline include: a lack of suitable sites for colonization
connected with a lack of adequate disturbance factors, competition from shading trees, and the presumed high age of the juniper
populations combined with zero generative reproduction. More than two thirds of the individuals showed slight damage to their
assimilation system. A health status of bad or very bad was determined for 5 % of the alpine juniper individuals. These trees
in the Hruby Jeseník Mts are also exposed to pressure from some herbivore insects and mammals. The populations are not yet
in a literally critical state, but considering the range of impacts affecting them, it will be necessary to pay significant
attention to their conservation strategies. Some recommendations for future management are suggested. 相似文献
53.
Polívka T van Stokkum IH Zigmantas D van Grondelle R Sundström V Hiller RG 《Biochemistry》2006,45(28):8516-8526
Carbonyl carotenoids are important constituents of the antenna complexes of marine organisms. These carotenoids possess an excited state with a charge-transfer character (intramolecular charge transfer state, ICT), but many details of the carotenoid to chlorophyll energy transfer mechanisms are as yet poorly understood. Here, we employ femtosecond transient absorption spectroscopy to study energy transfer pathways in the intrinsic light-harvesting complex (LHC) of dinoflagellates, which contains the carbonyl carotenoid peridinin. Carotenoid to chlorophyll energy transfer efficiency is about 90% in the 530-550 nm region, where the peridinin S2 state transfers energy with an efficiency of 25-50%. The rest proceeds via the S1/ICT channel, and the major S1/ICT-mediated energy transfer pathway utilizes the relaxed S1/ICT state and occurs with a time constant of 2.6 ps. Below 525 nm, the overall energy transfer efficiency drops because of light absorption by another carotenoid, diadinoxanthin, that contributes only marginally to energy transfer. Instead, its role is likely to be photoprotection. In addition to the peridinin-Chl-a energy transfer, it was shown that energy transfer also occurs between the two chlorophyll species in LHC, Chl-c2, and Chl-a. The time constant characterizing the Chl-c2 to Chl-a energy transfer is 1.4 ps. The results demonstrate that the properties of the S1/ICT state specific for carbonyl carotenoids is the key to ensure the effective harvesting of photons in the 500-600 nm region, which is of vital importance to underwater organisms. 相似文献
54.
A simple procedure basically applicable for the quantitative determination of activity of all restriction endonucleases is described. Native DNA immobilized on cellulose is used as a substrate; after the treatment by restriction endonucleases this DNA is released to the solution. Changes of the optical density of the solution containing solubilized DNA permit quantitative determination of the restriction endonuclease activity. 相似文献
55.
Veronika Okršlar Igor Plaper Maja Kovač Alenka Erjavec Tanja Obermajer Agata Rebec Maja Ravnikar Jana Žel 《In vitro cellular & developmental biology. Plant》2007,43(6):644-651
Roots of Primula veris L. contain considerable amounts of triterpene saponins, which are used in medicine as expectorants. P. veris is in many places an endangered plant, and its production in the field is laborious and a low yielding process. Plant tissue
culture provides an alternative means for producing secondary metabolites. Shoot apex, callus, suspension, and root cultures
of P. veris were developed for saponin production. In these cultures, the content of triterpene saponins, with focus on primula acid
I, the most dominant saponin in Primula species, was determined and compared to that in soil-grown plants. The highest content of primula acid I was observed in
root cultures, on average 29.5 mg/g dry weight. Some culture lines contained higher amounts of primula acid I (62.6 mg/g dry
weight) than the roots of plants grown in soil. 相似文献
56.
Camptothecin (CPT) is an anticancer drug that inhibits topoisomerase I (Topo I) by forming a ternary DNA-CPT-Topo I complex.
However, it has also been shown that UVA-irradiated CPT in the absence of Topo I produces significant DNA damage to cancer
cells. In this work, we explored and identified free radicals generated in these processes. From the low-temperature EPR spectrum
of Cu(II)-CPT complex, a proximity between Cu(II) ion and 20-hydroxy group of lactone E ring of CPT is proposed. Upon irradiation
(λ = 365 nm) of the Cu(II)-CPT complex in de-oxygenated dimethylsulfoxide (DMSO), the EPR signal of Cu(II) measured in situ
at room temperature shows formal first-order exponential decay with a formal half-life of 11 min. By the use of a specific
Cu(I) chelating agent, neocuproine, it was shown that, during this process, Cu(II) is reduced to Cu(I). The loss in EPR signal
intensity of the Cu(II)-CPT complex upon irradiation is accompanied by the appearance of a new EPR signal at g ≈ 2.0022. Application of the spin trap nitrosodurene (ND) revealed that the main radical product formed upon continuous irradiation
of CPT in DMSO solutions is the hydroxyl radical (trapped in DMSO as the •CH3 adduct) and superoxide radical. Application of 2,2,6,6-tetramethyl-4-piperidinol has revealed that irradiation of CPT in
aerated DMSO solution also leads to formation of singlet oxygen (1O2). Our spectroscopic experiments indicate that CPT is a promising photosensitizer and that radicals and singlet oxygen generated
upon illumination play a central role in DNA cleavage and in the induction of apoptosis in cancer cells. 相似文献
57.
Mrak P Podlesek Z van Putten JP Zgur-Bertok D 《Molecular genetics and genomics : MGG》2007,277(4):391-401
Phenotypic diversity provides populations of prokaryotic and eukaryotic organisms with the flexibility required to adapt to and/or survive environmental perturbations. Consequently, there is much interest in unraveling the molecular mechanisms of heterogeneity. A classical example of heterogeneity in Escherichia coli is the subset (3%) of the population that expresses the colicin K activity gene (cka) upon nutrient starvation. Here, we report on the mechanism underlying this variable response. As colicin synthesis is regulated by the LexA protein, the central regulator of the SOS response, we focused on the role of LexA and the SOS system in the variable cka expression. Real-time RT-PCR showed that the SOS system, without exogenous DNA damage, induces moderate levels of cka expression. The use of cka-gfp fusions demonstrated that modification of the conserved LexA boxes in the cka promoter region affected LexA binding affinity and the percentage of cka-gfp expressing cells in the population. A lexA-gfp fusion showed that the lexA gene is highly expressed in a subset of bacteria. Furthermore, cka-gfp fusions cloned into higher copy plasmid vectors increased the percentage of cka-gfp positive bacteria. Together, these results indicate that the bistability in cka expression in the bacterial population is determined by (1) basal SOS activity, (2) stochastic factors and possibly (3) the interplay of LexA dimers at cka operator. Other LexA regulated processes could exhibit similar regulation. 相似文献
58.
The information code in the temporal and spectral characteristics of the substrate-borne communication signals produced by
insects has been primarily studied in insects in the suborder Auchenorrhyncha. In the present study we investigated which
of the female calling song (FCS) parameters in Nezara viridula (L.) (Heteroptera, Pentatomidae) are essential for recognition by conspecific males. In playback experiments we measured
male vibrational responsiveness to FCS signals varying in the durations of pulse trains and inter-pulse train intervals, repetition
times, duty cycles, and dominant frequencies, and determined the preference range for each specific parameter. Males were
able to distinguish songs of different temporal and frequency parameters and responded best to values characteristic of the
song of conspecific females. Signal recognition is achieved on the basis of two temporal filters tuned to the durations of
the pulse train and inter-pulse train interval. Males responded best to the dominant frequency characteristic of conspecific
songs, which are tuned to the resonant properties of the herbaceous plants used for intraspecific signal transmission during
communication. 相似文献
59.
Soil structure stability was studied in every diagnostic horizons of six soil types (Haplic Chernozem, Greyic Phaeozem, two
Haplic Luvisols, Haplic Cambisol, Dystric Cambisol) using different techniques investigating various destruction mechanisms
of soil aggregates. Soil aggregate stability, assessed by the index of water stable aggregates (WSA), varied depending on the organic matter content, clay content and pHKCl. The presence of clay and organic matter coatings and fillings, and presence of iron oxides in some soils increased stability
of soil aggregates. On the other hand periodical tillage apparently decreased aggregate stability in the Ap horizons. Coefficients
of aggregate vulnerability resulting from fast wetting (KV
1) and slow wetting (KV
2) tests showed similar trends of the soil aggregate stability as the WSA index, when studied for soils developed on the similar parent material. There was found close correlation between the WSA index and the KV
1 value, which depended also on the organic matter content, clay content and pHKCl. Less significant correlation was obtained between the WSA index and the KV
2 value, which depended on the organic matter content and clay content. Coefficients of vulnerability resulting from the shaking
after pre-wetting test (KV
3) showed considerably different trends in comparison to the other tests due to the different factors affecting aggregate stability
against the mechanical destruction. The KV
3 value depended mostly on cation exchange capacity, pHKCl and organic matter content. 相似文献
60.
Fisher BJ Kraskauskas D Martin EJ Farkas D Wegelin JA Brophy D Ward KR Voelkel NF Fowler AA Natarajan R 《American journal of physiology. Lung cellular and molecular physiology》2012,303(1):L20-L32
Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis. 相似文献