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51.
Effect of three chlorinated pesticides on hsromega stress gene in transgenic Drosophila melanogaster
Expression of hsromega stress gene in the third-instar larvae of 951-lacZ2 (hsromega-lacZ having-844pb sequence) and 498-lacZ1 (hrsomega-lacZ having -498bp sequence) strains of Drosophila melanogaster at LC(50) and lower dietary concentrations of hexachlorocyclohexane (HCH) pentachlorophenol (PCP), and endosulfan was examined in relation to larval mortality by beta galactosidase activity, vital dye staining, and salivary gland polytene chromosome puffing. Our results showed that both HCH and PCP at lower concentrations evoked strong hsromega stress gene expression in the larval tissues while endosulfan did not. On the other hand, puffing data revealed that endosulfan at lower doses, induced well-developed puff at the resident site (93D) of the hsromega gene but the transgenic sites (30B in 951-lacZ2 and 44B in 498-lacZ1 strain) did not show any well-developed puff. Regression in hsromega stress gene expression in 951-lacZ2 strain at LC(50) concentrations of HCH and PCP after 48 h was concurrent with extensive tissue damage as evident by trypan blue staining. Similarly, strong hsromega expression was accompanied by insignificant trypan blue staining in the larval tissues of this strain after shorter duration of exposure (2-12 h) to these toxicants. Although endosulfan under similar experimental condition did not induce hsromega, strong trypan blue staining indicated extensive tissue damage after 48 h of exposure. The present study suggests that all the three toxicants pose cytotoxic potential to Drosophila. While protective role of this stress gene was evident at the initial stages of exposure, extensive tissue damage in the later stages of intoxication accompanied by autorepression of hsromega led to larval mortality. The study further suggests that -844bp upstream sequence of the gene is adequate for hsromega inducibility against HCH and PCP but not for endosulfan for which responsive elements may be searched further upstream. 相似文献
52.
Lisa A. Ridnour Sneha Dhanapal Michael Hoos Joan Wilson Jennifer Lee Robert Y. S. Cheng Ernst E. Brueggemann Harry B. Hines Donna M. Wilcock Michael P. Vitek David A. Wink Carol A. Colton 《Journal of neurochemistry》2012,123(5):736-749
Fibrillar amyloid plaques are largely composed of amyloid‐beta (Aβ) peptides that are metabolized into products, including Aβ1‐16, by proteases including matrix metalloproteinase 9 (MMP‐9). The balance between production and degradation of Aβ proteins is critical to amyloid accumulation and resulting disease. Regulation of MMP‐9 and its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP)‐1 by nitric oxide (NO) has been shown. We hypothesize that nitric oxide synthase (NOS2) protects against Alzheimer's disease pathology by increasing amyloid clearance through NO regulation of MMP‐9/TIMP‐1 balance. We show NO‐mediated increased MMP‐9/TIMP‐1 ratios enhanced the degradation of fibrillar Aβ in vitro, which was abolished when silenced for MMP‐9 protein translation. The in vivo relationship between MMP‐9, NO and Aβ degradation was examined by comparing an Alzheimer's disease mouse model that expresses NOS2 with a model lacking NOS2. To quantitate MMP‐9 mediated changes, we generated an antibody recognizing the Aβ1‐16 fragment, and used mass spectrometry multi‐reaction monitoring assay for detection of immunoprecipitated Aβ1‐16 peptides. Aβ1‐16 levels decreased in brain lysates lacking NOS2 when compared with strains that express human amyloid precursor protein on the NOS2 background. TIMP‐1 increased in the APPSwDI/NOS2?/? mice with decreased MMP activity and increased amyloid burden, thereby supporting roles for NO in the regulation of MMP/TIMP balance and plaque clearance. 相似文献
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56.
黄硕陈健贾谊君王永坤陆云姝吴克瑾 《现代生物医学进展》2014,14(5):881-884
目的:研究三阴性乳腺癌(triple negative breast cancer,TNBC)中基质金属蛋白酶9(matrix metal proteinase 9,MMP9)和P53的表达及其与三阴性乳腺癌预后的关系。方法:收集2002年3月至2011年7月上海交通大学医学院附属新华医院普外科诊治且临床资料完整的TNBC标本147例,通过免疫组化检测其MMP9、P53的表达。结合临床随访数据,分析MMP9、P53的表达与TNBC预后的关系。结果:TNBC占同期本院收治的乳腺癌13.3%(147/1103)。MMP9、P53在TNBC中的阳性表达率分别为47.6%和66.0%。MMP9与TNBC患者的淋巴结转移数显著相关(P=0.003)。MMP9表达阳性的TNBC与MMP9表达阴性TNBC患者60个月的无病生存(disease free survival,DFS)率分别为62%和83%,差异具有统计学意义(P=0.001);总体生存率(overall survival,OS)率分别为66%和73%,差异具有统计学意义(P=0.022)。P53表达阳性的TNBC和P53表达阴性的TNBC患者60个月的DFS分别为65%和87%(P=0.010);OS分别为60%和85%(P=0.005)。MMP9和P53的HR分别为3.353(95%CI:1.614-6.966,P=0.001)和2.979(95%CI:1.239-7.165,P=0.015)。结论:MMP9和P53在TNBC中的阳性表达与患者的预后不良有关,且MMP9为影响TNBC患者预后的独立危险因素。 相似文献
57.
Håkansson M Svensson A Fast J Linse S 《Protein science : a publication of the Protein Society》2001,10(5):927-933
The structure of calbindin D(9k) with two substitutions was determined by X-ray crystallography at 1.8-A resolution. Unlike wild-type calbindin D(9k), which is a monomeric protein with two EF-hands, the structure of the mutated calbindin D(9k) reveals an intertwined dimer. In the dimer, two EF-hands of the monomers have exchanged places, and thus a 3D domain-swapped dimer has been formed. EF-hand I of molecule A is packed toward EF-hand II of molecule B and vice versa. The formation of a hydrophobic cluster, in a region linking the EF-hands, promotes the conversion of monomers to 3D domain-swapped dimers. We propose a mechanism by which domain swapping takes place via the apo form of calbindin D(9k). Once formed, the calbindin D(9k) dimers are remarkably stable, as with even larger misfolded aggregates like amyloids. Thus calbindin D(9k) dimers cannot be converted to monomers by dilution. However, heating can be used for conversion, indicating high energy barriers separating monomers from dimers. 相似文献
58.
Substrate inhibition is a common phenomenon in enzyme chemistry, which is observed only with a fast-reacting substrate enantiomer. We report here for the first time substrate inhibition of an enantioselective enzyme by both substrate enantiomers. The enantioselective substrate inhibition, i.e., different mode of inhibition by each substrate enantiomer, of (S)-specific omega-transaminase was found with various chiral amines. A kinetic model based on ping-pong bi-bi mechanism has been developed and kinetic parameters were measured. The kinetic model reveals that the inhibition by (R)-amine results from formation of Michaelis complex with enzyme-pyridoxal 5'-phosphate, whereas the inhibition by (S)-amine results from the formation of the complex with enzyme-pyridoxamine 5'-phosphate. Substrate inhibition constants (K(SI)) of each (S)-enantiomer of four chiral amines showed a linear correlation with those of cognate (R)-amines. Such a correlation was also found between the K(SI) values and Michaelis constants of (S)-amines. These correlations indicate that recognition mechanisms and active site structures of both enzyme-pyridoxal 5'-phosphate, enzyme-pyridoxamine 5'-phosphate are similar. Taken together with the results, high propensity for non-productive substrate binding strongly suggests that binding pockets of the omega-transaminase is loosely defined, which accounts for the enantioselective substrate inhibition. 相似文献
59.
Abstract: A synthetic peptide corresponding to residues 226–240 (E9 peptide) of human τ, which contains an Lys-Ser-Pro motif, was used to raise a polyclonal antibody. The antibody, E9, was 10-fold less reactive with phospho-E9 peptide than with native E9 peptide. E9 antibody was used to study the extent of phosphorylation in a modified form of τ (PHF-τ) that is found in Alzheimer's disease brain and is incorporated into paired helical filaments (PHFs). E9 immunolabeled Alzheimer's disease neurofibrillary tangles and abnormal neurites in brain sections intensely, with increased immunoreactivity detected after pretreatment of sections with phosphatase. On immunoblots and ELISA, E9 reacted with PHF-τ and recombinant human τ but not with the high and middle molecular weight neurofilament proteins. Phosphatase treatment of PHF-τ improved the E9 immunoreactivity by 30–50%. Dephosphorylated high but not middle molecular weight neurofilament protein became reactive with E9. These results indicate that <50% of the PHF-T is phosphorylated in the subregion corresponding to residues 226–240 of τ and suggest that the phosphorylation of this region may not be essential for PHF formation. 相似文献
60.
A. Herchuelz P. Lebrun A. Carpinelli N. Thonnart A. Sener W.J. Malaisse 《生物化学与生物物理学报:生物膜》1981,640(1):16-30
The effects of quinine and 9-aminoacridine, two blockers of potassium conductance in islet cells, on 45Ca efflux and insulin release from perifused islets were investigated in order to elucidate the mechanisms by which glucose initially reduces 45Ca efflux and later stimulates calcium inflow in islet cells. In the absence of glucose, 100 μM quinine stimulated 45Ca net uptake, 45Ca outflow rate and insulin release. Quinine also dramatically enhanced the cationic and the secretory response to intermediate concentrations of glucose, but had little effect on 45Ca net uptake, 45Ca fractional outflow rate and insulin release at a high glucose concentration (16.7 mM). The ability of quinine to stimulate 45Ca efflux depended on the presence of extracellular calcium, suggesting that it reflects a stimulation of calcium entry in the islet cells. In the absence of extracellular calcium, quinine provoked a sustained decrease in 45Ca efflux. Such an inhibitory effect was not additive to that of glucose, and was reduced at low extracellular Na+ concentration. At a low concentration (5 μM), quinine, although reducing 86Rb efflux from the islets to the same extent as a non-insulinotropic glucose concentration (4.4 mM), failed to inhibit 45Ca efflux. In the presence of extracellular calcium, 9-aminoacridine produced an important but transient increase in 45Ca outflow rate and insulin release from islets perifused in the absence of glucose. In the absence of extracellular calcium, 9-aminoacridine, however, failed to reduced 45Ca efflux from perifused islets. It is concluded that quinine, by reducing K+ conductance, reproduces the effect of glucose to activate voltage-sensitive calcium channels and to stimulate the entry of calcium into the B-cell. However, the glucose-induced inhibition of calcium outflow rate, which may also participate in the intracellular accumulation of calcium, does not appear to be mediated by changes in K+ conductance. 相似文献