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171.
Liao P Yu D Li G Yong TF Soon JL Chua YL Soong TW 《The Journal of biological chemistry》2007,282(48):35133-35142
Native smooth muscle L-type Ca(v)1.2 calcium channels have been shown to support a fraction of Ca(2+) currents with a window current that is close to resting potential. The smooth muscle L-type Ca(2+) channels are also more susceptible to inhibition by dihydropyridines (DHPs) than the cardiac channels. It was hypothesized that smooth muscle Ca(v)1.2 channels exhibiting hyperpolarized shift in steady-state inactivation would contribute to larger inhibition by DHP, in addition to structural differences of the channels generated by alternative splicing that modulate DHP sensitivities. In addition, it has also been shown that alternative splicing modulates DHP sensitivities by generating structural differences in the Ca(v)1.2 channels. Here, we report a smooth muscle L-type Ca(v)1.2 calcium channel splice variant, Ca(v)1.2SM (1/8/9(*)/32/Delta33), that when expressed in HEK 293 cells display hyperpolarized shifts for steady-state inactivation and activation potentials when compared with the established Ca(v)1.2b clone (1/8/9(*)/32/33). This variant activates from more negative potentials and generates a window current closer to resting membrane potential. We also identified the predominant cardiac isoform Ca(v)1.2CM clone (1a/8a/Delta9(*)/32/33) that is different from the established Ca(v)1.2a (1a/8a/Delta9(*)/31/33). Importantly, Ca(v)1.2SM channels were shown to be more sensitive to nifedipine blockade than Ca(v)1.2b and cardiac Ca(v)1.2CM channels when currents were recorded in either 5 mM Ba(2+) or 1.8 mM Ca(2+) external solutions. This is the first time that a smooth muscle Ca(v)1.2 splice variant has been identified functionally to possess biophysical property that can be linked to enhanced state-dependent block by DHP. 相似文献
172.
173.
Structural and functional analyses of disease-causing missense mutations in Bloom syndrome protein 总被引:1,自引:0,他引:1
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Guo RB Rigolet P Ren H Zhang B Zhang XD Dou SX Wang PY Amor-Gueret M Xi XG 《Nucleic acids research》2007,35(18):6297-6310
Bloom syndrome (BS) is an autosomal recessive disorder characterized by genomic instability and the early development of many types of cancer. Missense mutations have been identified in the BLM gene (encoding a RecQ helicase) in affected individuals, but the molecular mechanism and the structural basis of the effects of these mutations remain to be elucidated. We analysed five disease-causing missense mutations that are localized in the BLM helicase core region: Q672R, I841T, C878R, G891E and C901Y. The disease-causing mutants had low ATPase and helicase activities but their ATP binding abilities were normal, except for Q672, whose ATP binding activity was lower than that of the intact BLM helicase. Mutants C878R, mapping near motif IV, and G891E and C901Y, mapping in motif IV, displayed severe DNA-binding defects. We used molecular modelling to analyse these mutations. Our work provides insights into the molecular basis of BLM pathology, and reveals structural elements implicated in coupling DNA binding to ATP hydrolysis and DNA unwinding. Our findings will help to explain the mechanism underlying BLM catalysis and interpreting new BLM causing mutations identified in the future. 相似文献
174.
Effects of hydrodynamics on phosphorus concentrations in water of Lake Taihu,a large,shallow, eutrophic lake of China 总被引:4,自引:0,他引:4
Guangwei Zhu Boqiang Qin Guang Gao Lu Zhang Liancong Luo Yunlin Zhang 《Hydrobiologia》2007,581(1):53-61
To understand the effect of hydrodynamical process on water phosphorus concentration, wind, wave, and several water quality
indices were observed in Meiliang Bay, a shallow and eutrophic bay locates in north of Lake Taihu. During the 7 day observation
period, wind speed and significant wave height were recorded more than 3 h per day, and water samples were collected in five
water-depth layers once a day. Hydrodynamical disturbance had no significant correlationship with the water quality at the
top layer when the significant wave height was smaller than 30 cm, but it significantly increased suspended solids (SS) concentration
of the bottom water layer. Concentrations of nutrients showed no positive correlationship with SS concentration in the water
body. Intensive sediment resuspension may not have occurred when the hydrodynamic stress on sediment was only a little higher
than the critical stress for sediment resuspension. A new method for confirming the critical stress for intensive sediment
resuspension and nutrient release still needs to be developed. The range of the water quality indices was quite high during
the seven days of observation. High variation seems to be a common character of large shallow lakes like Taihu. 相似文献
175.
A tetrameric [Ag(μ-3,5-tBu2pz)]4 · CH2Cl2 (1 · CH2Cl2) has been prepared and structurally characterized. The four Ag-atoms are in an approximate rhombic arrangement with pyrazolato bridges alternating on either side of the Ag4-plane. A 1H NMR study shows partial decomposition of 1 to the mononuclear [Ag(3,5-tBu2pzH)2]+ in solution. 相似文献
176.
目的获取可应用于静脉血管组织工程的种子细胞内皮细胞。方法选取北京地区雄性杂种犬,取其双侧颈外静脉,采用翻转后酶消法,获取原代内皮细胞,对其进行原代培养和传代培养,冻存、复苏和鉴定,并利用光学显微镜进行观察。结果获取犬的颈外静脉后,实验采取了翻转后酶消法,所获得的内皮细胞纯度和数量得到了提高;经过鉴定确实为内皮细胞来源;活性好,增殖快,在较短的时间内能够达到后期实验所需数量。结论经体外培养的犬的颈外静脉内皮细胞可以作为组织工程血管的种子细胞。 相似文献
177.
验证了荧光假单胞菌(Pseudomonas fluorescensATCC13525)香兰素脱氢酶基因(vanillin dehydrogenasegene,vdh)的功能。基因vdh表达产物(Vdh)的活性测定结果显示Vdh具有很高的活性,而且不经IPTG诱导的Vdh也具有同样高的活性。经过4 h的体外酶促反应,重组蛋白Vdh能把95%以上的香兰素转化为香兰素酸,从而验证了vdh基因的表达产物具有香兰素脱氢酶的功能。同时发现NAD 是从香兰素到香兰素酸体外转化必不可少的因素。 相似文献
178.
Curcumin induces apoptosis through mitochondrial hyperpolarization and mtDNA damage in human hepatoma G2 cells 总被引:4,自引:0,他引:4
Cao J Liu Y Jia L Zhou HM Kong Y Yang G Jiang LP Li QJ Zhong LF 《Free radical biology & medicine》2007,43(6):968-975
Curcumin, a major pigment of turmeric, is a natural antioxidant possessing a variety of pharmacological activities and therapeutic properties. But its mechanisms are unknown. In our previous study, we found that a 2-h exposure to curcumin induced DNA damage to both the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA) in HepG2 cells and that mtDNA damage was more extensive than nDNA damage. Therefore, experiments were initiated to evaluate the role of mtDNA damage in curcumin-induced apoptosis. The results demonstrated that HepG2 cells challenged with curcumin for 1 h showed a transient elevation of the mitochondrial membrane potential (DeltaPsim), followed by cytochrome c release into the cytosol and disruption of DeltaPsim after 6 h exposure to curcumin. Apoptosis was detected by Hoechst 33342 and annexin V/PI assay after 10 h treatment. Interestingly, the expression of Bcl-2 remained unchanged. A resistance to apoptosis for the corresponding rho0 counterparts confirmed a critical dependency for mitochondria during the induction of apoptosis in HepG2 cells mediated by curcumin. The effects of PEG-SOD in protecting against curcumin-induced cytotoxicity suggest that curcumin-induced cytotoxicity is directly dependent on superoxide anion O2- production. These data suggest that mitochondrial hyperpolarization is a prerequisite for curcumin-induced apoptosis and that mtDNA damage is the initial event triggering a chain of events leading to apoptosis in HepG2 cells. 相似文献
179.
In this study, we attempt to improve the prediction of mutation position in H5N1 hemagglutinin from influenza A virus using the neural network model with distinguishing of arginine, leucine and serine. In comparison with previous logistic regression prediction model, the 3-6-1 feedforward back propagation neural network model reduced independents from seven to three without compromising the predictability, and the prediction is made according to the most similar parameterised hemagglutinin rather than the population means. 相似文献
180.
Long Jun-Yi Wang Xue-Jun Li Xiao-Ying Kong Xie-He Yang Guang Zhang Dan Yang Yan-Ting Shi Zheng Ma Xiao-Peng 《Neurochemical research》2022,47(3):545-551
Neurochemical Research - Chronic visceral pain (CVP) is one of the common symptoms of many diseases triggered by underlying diseases of the internal organs of the human body. Its causes include... 相似文献