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61.
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Role of ERAB/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Abeta-induced cytotoxicity
SD Yan Y Shi A Zhu J Fu H Zhu Y Zhu L Gibson E Stern K Collison F Al-Mohanna S Ogawa A Roher SG Clarke DM Stern 《Canadian Metallurgical Quarterly》1999,274(4):2145-2156
Endoplasmic reticulum-associated amyloid beta-peptide (Abeta)-binding protein (ERAB)/L-3-hydroxyacyl-CoA dehydrogenase type II (HADH II) is expressed at high levels in Alzheimer's disease (AD)-affected brain, binds Abeta, and contributes to Abeta-induced cytotoxicity. Purified recombinant ERAB/HADH II catalyzed the NADH-dependent reduction of S-acetoacetyl-CoA with a Km of approximately 68 microM and a Vmax of approximately 430 micromol/min/mg. The contribution of ERAB/HADH II enzymatic activity to Abeta-mediated cellular dysfunction was studied by site-directed mutagenesis in the catalytic domain (Y168G/K172G). Although COS cells cotransfected to overexpress wild-type ERAB/HADH II and variant beta-amyloid precursor protein (betaAPP(V717G)) showed DNA fragmentation, cotransfection with Y168G/K172G-altered ERAB and betaAPP(V717G) was without effect. We thus asked whether the enzyme might recognize alcohol substrates of which the aldehyde products could be cytotoxic; ERAB/HADH II catalyzed oxidation of a variety of simple alcohols (C2-C10) to their respective aldehydes in the presence of NAD+ and NAD-dependent oxidation of 17beta-estradiol. Addition of micromolar levels of synthetic Abeta(1-40) to purified ERAB/HADH II inhibited, in parallel, reduction of S-acetoacetyl-CoA (Ki approximately 1.6 microM), as well as oxidation of 17beta-estradiol (Ki approximately 3.2 microM) and (-)-2-octanol (Ki approximately 2.6 microM). Because micromolar levels of Abeta were required to inhibit ERAB/HADH II activity, whereas Abeta binding to ERAB/HADH II occurred at much lower concentrations (Km approximately 40-70 nM), the latter more closely simulating Abeta levels within cells, Abeta perturbation of ERAB/HADH II was likely to result from mechanisms other than the direct modulation of enzymatic activity. Cells cotransfected to overexpress ERAB/HADH II and betaAPP(V717G) generated malondialdehyde-protein and 4-hydroxynonenal-protein epitopes, which were detectable only at the lowest levels in cells overexpressing either ERAB/HADH II or betaAPP(V717G) alone. Generation of such toxic aldehydes was not observed in cells contransfected to overexpress Y168G/K172G-altered ERAB and betaAPP(V717G). We conclude that the generalized alcohol dehydrogenase activity of ERAB/HADH II is central to the cytotoxicity observed in an Abeta-rich environment. 相似文献
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核电在改善空气质量方面具有重要的作用。本文对比了核电与煤电的空气污染物排放系数,根据空气污染物引起的死亡率与人均燃煤发电量的负指数幂关系,评估了中国通过发展核电在改善空气质量方面对居民的健康效益,并对未来的健康效益进行了分析。结果显示,发展核电能够避免的死亡人数在增加。据估算,1995—2018年,中国核电累计可避免约4.7万人因空气污染物死亡,可避免约22.6万人因空气污染物患病。2020—2030年,预计会避免8.3万~9.4万人死亡,避免39.7万~45.1万人患病。 相似文献
65.
WuGang HeZhen-Li 《核技术(英文版)》1998,9(3):176-180
The influence of fertilization with urea and ryegrass on nitrogen utilization and transformation in red soil has been studied by using ^15N tracer method.When urea and ryegrass were applied alone or in combination,the percentage of N uptaken by ryegrass from labelled urea was 3 and 1.7 times that from labelled ryegrass for the application rate of 200mgN.kg^-1 and 100mgN.kg^-1,respectively;combining application of ryegrass and ureareduced uptake of urea N and increased uptake of ryegrass N by ryegrass plant,but the percentage of N residued in soil increased for urea and decreased for ryegrass.when urea and ryegrass were applied alone,the percentage of N residued in soil from labelled ryegrass was more than 69% while that from labelled urea was less than 25%,and much more ryegrass N was incorporated into humus than urea N. 相似文献
66.
管府 《兰州工业高等专科学校学报》2011,(6):35-38
结合我国某高铁预应力混凝土简支箱梁采用后张法施工的过程,简要论述三项关键工序、高性能混凝土耐久性指标的保证措施、减小箱梁后期徐变的相关施工措施及注意要点,以确保满足高速铁路运营的安全性、高速度、高平顺性和舒适度. 相似文献
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