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排序方式: 共有157条查询结果,搜索用时 390 毫秒
81.
82.
Abu-Hamad S Zaid H Israelson A Nahon E Shoshan-Barmatz V 《The Journal of biological chemistry》2008,283(19):13482-13490
In brain and tumor cells, the hexokinase isoforms HK-I and HK-II bind to the voltage-dependent anion channel (VDAC) in the outer mitochondrial membrane. We have previously shown that HK-I decreases murine VDAC1 (mVDAC1) channel conductance, inhibits cytochrome c release, and protects against apoptotic cell death. Now, we define mVDAC1 residues, found in two cytoplasmic domains, involved in the interaction with HK-I. Protection against cell death by HK-I, as induced by overexpression of native or mutated mVDAC1, served to identify the mVDAC1 amino acids required for interaction with HK-I. HK-I binding to mVDAC1 either in isolated mitochondria or reconstituted in a bilayer was inhibited upon mutation of specific VDAC1 residues. HK-I anti-apoptotic activity was also diminished upon mutation of these amino acids. HK-I-mediated inhibition of cytochrome c release induced by staurosporine was also diminished in cells expressing VDAC1 mutants. Our results thus offer new insights into the mechanism by which HK-I promotes tumor cell survival via inhibition of cytochrome c release through HK-I binding to VDAC1. These results, moreover, point to VDAC1 as a key player in mitochondrially mediated apoptosis and implicate an HK-I-VDAC1 interaction in the regulation of apoptosis. Finally, these findings suggest that interference with the binding of HK-I to mitochondria by VDAC1-derived peptides may offer a novel strategy by which to potentiate the efficacy of conventional chemotherapeutic agents. 相似文献
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Many tumorigenic p53 mutants gain a common antigenic epitope that is recognized by the PAb-240 antibody. Database search identified the presence of this epitope in several other proteins, including several antibodies and the catalytic subunit of mouse telomerase, mTERT. These antibodies may represent a part of the previously demonstrated anti-idiotypic network built around p53. In the present study we demonstrate that the PAb-240 antibody was able to inhibit telomerase activity in extracts from both mouse and human tumor cells. The recognition of mTERT by PAb-240 is demonstrated by Western blotting and by using blocking peptides derived from mTERT. The existence of a shared epitope between mutant p53 and telomerase may suggest that the two proteins contribute to malignant transformation through a common pathway. 相似文献
85.
Ben-Zeev B Levy-Nissenbaum E Lahat H Anikster Y Shinar Y Brand N Gross-Tzur V MacGregor D Sidi R Kleta R Frydman M Pras E 《Human genetics》2002,111(2):214-218
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive inherited neurological disorder characterized by macrocephaly, deterioration in motor functions and cerebellar ataxia. In Israel the disease is found in an increased frequency among Libyan Jews. The disease is caused by mutations in the MLC1 gene, which encodes a putative CNS membrane transporter. We describe three novel mutations (p.G59E, p.P92S, and 134_136insC) in seven MLC families. One of these mutations, p.G59E, was found in the vast majority of MLC patients in Israel. Screening of 200 normal Libyan Jewish individuals for the p.G59E mutation, revealed a carrier rate of 1/40 compared with an expected carrier rate of 1/81. Several explanations could account for this difference the most likely one is an admixture of the Libyan Jewish population. 相似文献
86.
The synaptic vesicle protein synaptophysin: purification and characterization of its channel activity 总被引:1,自引:0,他引:1
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The synaptic vesicle protein synaptophysin was solubilized from rat brain synaptosomes with a relatively low concentration of Triton X-100 (0.2%) and was highly purified (above 95%) using a rapid single chromatography step on hydroxyapatite/celite resin. Purified synaptophysin was reconstituted into a planar lipid bilayer and the channel activity of synaptophysin was characterized. In asymmetric KCl solutions (cis 300 mM/trans 100 mM), synaptophysin formed a fast-fluctuating channel with a conductance of 414 +/- 13 pS at +60 mV. The open probability of synaptophysin channels was decreased upon depolarization, and channels were found to be cation-selective. Synaptophysin channels showed higher selectivity for K(+) over Cl(-) (P(K(+))/P(Cl(-)) > 8) and preferred K(+) over Li(+), Na(+), Rb(+), Cs(+), or choline(+). The synaptophysin channel is impermeable to Ca(2+), which has no effect on its channel activity. This study is the second demonstration of purified synaptophysin channel activity, but the first biophysical characterization of its channel properties. The availability of large amounts of purified synaptophysin and of its characteristic channel properties might help to establish the role of synaptophysin in synaptic transmission. 相似文献
87.
An early transient increase in brain polyamine (PA) metabolism, termed the PA-stress-response (PSR), is a common reaction to stressful stimuli, including physical, emotional, and hormonal stressors, with a magnitude related to the stress intensity. In the extreme, traumatic injury can result in an incomplete PSR, with persistent accumulation of putrescine and eventual reduction in the concentrations of the higher polyamines (PAs), spermidine and spermine. Chronic intermittent application of stressors causes a recurrence of the brain PSR, but, in contrast, it leads to habituation of the response in the periphery (liver). Severe continuous stress, however, may lead to accumulation of brain PAs. Long-term inhibition of PA synthesis depletes brain PAs and can result in altered emotional reactivity to stressors. Furthermore, the brain PSR, in contrast to the periphery, can be blocked by a long-term, but not by short-term, treatment with lithium, the most efficacious treatment of manic–depressive illness. The brain PSR is developmentally regulated, and the switch to the mature pattern coincides with the cessation of the stress hyporesponsive period in the hypothalamic–pituitary–adrenocortical (HPA) system. In contrast to the brain and liver, the PSR in the adrenal and thymus is down-regulated by acute stressors. Transient up-regulation of the PSR, as in the brain and liver, is implicated in cell survival while its down-regulation is implicated in cell death. Taken together, the findings indicate that the PSR is a dynamic process that varies with the type, intensity, and duration of stressors, and implicate this response as an adaptive mechanism in the reaction to stressful events. Under persistent stressful conditions, however, the PSR may be maladaptive as may be reflected by PA accumulation. This raises the hypothesis that proper regulation of brain PSR may be critical for neuronal function and for an appropriate behavioral response to stressors. 相似文献
88.
89.
Gincel D Silberberg SD Shoshan-Barmatz V 《Journal of bioenergetics and biomembranes》2000,32(6):571-583
The voltage-dependent anion channel (VDAC), also known as mitochondrial porin, is a large channel permeable to anions, cations, ATP, and other metabolites. VDAC was purified from sheep brain synaptosomes or rat liver mitochondria using a reactive red-agarose column, in addition to the hydroxyapatitate column. The red-agarose column allowed further purification (over 98%), concentration of the protein over ten-fold, decreasing Triton X-100 concentration, and/or replacing Triton X-100 with other detergents, such as Nonidet P-40 or octylglucoside. This purified VDAC reconstituted into planar-lipid bilayer, had a unitary maximal conductance of 3.7 ± 0.1 nS in 1 M NaCl, at 10 mV and was permeable to both large cations and anions. In the maximal conducting state, the permeability ratios for Na+, acetylcholine+, dopamine,+ and glutamate–, relative to Cl–, were estimated to be 0.73, 0.6, 0.44, and 0.4, respectively. In contrast, in the subconducting state, glutamate– was impermeable, while the relative permeability to acetylcholine+ increased and to dopamine+ remained unchanged. At the high concentrations (0.1–0.5 M) used in the permeability experiments, glutamate eliminated the bell shape of the voltage dependence of VDAC channel conductance. Glutamate at concentrations of 1 to 20 mM, in the presence of 1 M NaCl, was found to modulate the VDAC channel activity. In single-channel experiments, at low voltages (±10 mV), glutamate induced rapid fluctuations of the channel between the fully open state and long-lived low-conducting states or short-lived closed state. Glutamate modification of the channel activity, at low voltages, is dependent on voltage, requiring short-time (20–60 sec) exposure of the channel to high membrane potentials. The effect of glutamate is specific, since it was observed in the presence of 1 M NaCl and it was not obtained with aspartate or GABA. These results suggest that VDAC possesses a specific glutamate-binding site that modulates its activity. 相似文献
90.