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391.
Alexander V. Zhdanov Ruslan I. Dmitriev Dmitri B. Papkovsky 《Cellular and molecular life sciences : CMLS》2011,68(5):903-917
Bafilomycin A1 (Baf) induces an elevation of cytosolic Ca2+ and acidification in neuronal cells via inhibition of the V-ATPase. Also, Baf uncouples mitochondria in differentiated PC12
(dPC12), dSH-SY5Y cells and cerebellar granule neurons, and markedly elevates their respiration. This respiratory response in dPC12 is accompanied by morphological changes in the mitochondria and decreases the mitochondrial pH, Ca2+ and ΔΨm. The response to Baf is regulated by cytosolic Ca2+ fluxes from the endoplasmic reticulum. Inhibition of permeability transition pore opening increases the depolarizing effect
of Baf on the ΔΨm. Baf induces stochastic flickering of the ΔΨm with a period of 20 ± 10 s. Under conditions of suppressed
ATP production by glycolysis, oxidative phosphorylation impaired by Baf does not provide cells with sufficient ATP levels.
Cells treated with Baf become more susceptible to excitation with KCl. Such mitochondrial uncoupling may play a role in a
number of (patho)physiological conditions induced by Baf. 相似文献
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393.
Neurotransmitter release at synapses between nerve cells is mediated by calcium-triggered exocytotic fusion of synaptic vesicles. Before fusion, vesicles dock at the presynaptic release site where they mature to a fusion-competent state. Here we identify Munc13-1, a brain-specific presynaptic phorbol ester receptor, as an essential protein for synaptic vesicle maturation. We show that glutamatergic hippocampal neurons from mice lacking Munc13-1 form ultrastructurally normal synapses whose synaptic-vesicle cycle is arrested at the maturation step. Transmitter release from mutant synapses cannot be triggered by action potentials, calcium-ionophores or hypertonic sucrose solution. In contrast, release evoked by alpha-latrotoxin is indistinguishable from wild-type controls, indicating that the toxin can bypass Munc13-1-mediated vesicle maturation. A small subpopulation of synapses of any given glutamatergic neuron as well as all synapses of GABA (gamma-aminobutyric acid)-containing neurons are unaffected by Munc13-1 loss, demonstrating the existence of multiple and transmitter-specific synaptic vesicle maturation processes in synapses. 相似文献
394.
G S Jimenez F Bryntesson M I Torres-Arzayus A Priestley M Beeche S Saito K Sakaguchi E Appella P A Jeggo G E Taccioli G M Wahl M Hubank 《Nature》1999,400(6739):81-83
Damage to DNA in the cell activates the tumour-suppressor protein p53, and failure of this activation leads to genetic instability and a predisposition to cancer. It is therefore crucial to understand the signal transduction mechanisms that connect DNA damage with p53 activation. The enzyme known as DNA-dependent protein kinase (DNA-PK) has been proposed to be an essential activator of p53, but the evidence for its involvement in this pathway is controversial. We now show that the p53 response is fully functional in primary mouse embryonic fibroblasts lacking DNA-PK: irradiation-induced DNA damage in these defective fibroblasts induces a normal response of p53 accumulation, phosphorylation of a p53 serine residue at position 15, nuclear localization and binding to DNA of p53. The upregulation of p53-target genes and cell-cycle arrest also occur normally. The DNA-PK-deficient cell line SCGR11 contains a homozygous mutation in the DNA-binding domain of p53, which may explain the defective response by p53 reported in this line. Our results indicate that DNA-PK activity is not required for cells to mount a p53-dependent response to DNA damage. 相似文献
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397.
为了能够快速准确的评定预应力管道的灌浆质量,采用IES(Impact-Echo System)扫描式冲击回波测试系统,对阿荣旗至北海省际通道支线赤峰-大板高速公路预应力箱梁管道灌浆施工质量进行评估。结果表明采用该种方法能够较好地评定预应力管道灌浆质量,对质量不合格的部位作出及时处理,以保证结构安全。 相似文献
398.
Targets of homeotic gene control in Drosophila 总被引:18,自引:0,他引:18
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400.
A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. 总被引:46,自引:0,他引:46
P Basset J P Bellocq C Wolf I Stoll P Hutin J M Limacher O L Podhajcer M P Chenard M C Rio P Chambon 《Nature》1990,348(6303):699-704
A gene has been identified that is expressed specifically in stromal cells surrounding invasive breast carcinomas. On the basis of its sequence, the product of this gene, named stromelysin-3, is a new member of the family of metalloproteinase enzymes which degrade the extracellular matrix. The suggestion is that stromelysin-3 is one of the stroma-derived factors that have long been postulated to play an important part in progression of epithelial malignancies. 相似文献