4-Hydroxynonenal-modified amyloid-beta peptide inhibits the proteasome: possible importance in Alzheimer's disease

The amyloid β-peptide (Aβ) is a 4-kDa species derived from the amyloid precursor protein, which accumulates in the brains of patients with Alzheimer’s disease. Although we lack full understanding of the etiology and pathogenesis of selective neuron death, considerable data do imply roles for both the toxic Aβ and increased oxidative stress. Another significant observation is the accumulation of abnormal, ubiquitin-conjugated proteins in affected neurons, suggesting dysfunction of the proteasome proteolytic system in these cells. Recent reports have indicated that Aβ can bind and inhibit the proteasome, the major cytoslic protease for degrading damaged and ubiquitin-conjugated proteins. Earlier results from our laboratory showed that moderately oxidized proteins are preferentially recognized and degraded by the proteasome; however, severely oxidized proteins cannot be easily degraded and, instead, inhibit the proteasome. We hypothesized that oxidatively modified Aβ might have a stronger (or weaker) inhibitory effect on the proteasome than does native Aβ. We therefore also investigated the proteasome inhibitory action of Aβ _1–40 (a peptide comprising the first 40 residues of Aβ) modified by the intracellular oxidant hydrogen peroxide, and by the lipid peroxidation product 4-hydroxynonenal (HNE). H₂O₂ modification of Aβ _1–40 generates a progressively poorer inhibitor of the purified human 20S proteasome. In contrast, HNE modification of Aβ _1–40 generates a progressively more selective and efficient inhibitor of the degradation of fluorogenic peptides and oxidized protein substrates by human 20S proteasome. This interaction may contribute to certain pathological manifestations of Alzheimer’s disease Received 26 September 2000; accepted 26 September 2000     

纳米硅对三峡库区柑橘青霉菌的药效试验

对三峡库区柑橘果实贮藏期间携带微生物进行了分离,青霉菌(Penicillium)为主要的致病菌;不同药剂处理接种青霉菌的柑橘果实,实验表明多菌灵抑菌效果最好,防效达到65.4%,其次是纳米硅达到53.4%;对青霉菌的抑菌■试验表明,多菌灵抑制效果最好,抑制率为90%,纳米硅为88%.说明纳米硅对柑橘青霉病有一定的防治效果,并因其无公害有施用价值.     

周口店北京人遗址环境地质条件及地质病害机理分析

自周口店北京人遗址区被发现后的几十年以来,由于自然和人为因素的影响,在各发掘点内出现了诸多不同类型的地质病害,严重威胁着遗址区的安全与保护.基于此,通过现场及室内试验对遗址区环境工程地质条件进行了分析并在此基础上通过岩石薄片镜下鉴定、岩石化学分析及崩解试验等对影响遗址区病害的因素及机理做了分析.结果发现,周口店遗址区7个发掘点共有20处类型不一、规模不等、变形程度不同的潜在地质病害点.其破坏的原因可以归结为地质、环境及人类活动3个因素,其中着重讨论了环境因素的影响.环境因素分析结果表明,不同地点处由于其胶结物成份不同所以环境因素对其的影响方式也不同.图12,表3,参8.     

宋代的牲畜疫病及政府的应对——以宋代政府诏令为中心的讨论

历代政府对耕牛和马都给予了保护性的政策。两宋时期,耕牛和马作为农业生产的主要动力与运输工具,由于国营牧监的南移和饲养方式的变化,导致了疫病的频繁发生和流行,从而引起了宋代政府的高度重视。以宋代政府诏令为中心,探讨宋代牲畜疫病的流行情况及特点,牲畜疫病的病因及对农业生产、交通运输和军事战争所产生的重大影响,分析和疏理宋代通过政府诏令对不同时期发生的牲畜疫病所采取的应对措施。同时,还探讨北宋和南宋政府在牲畜疫病应对上的不同,以及这种不同与两宋时期的政治军事和社会经济之间的关系。     

开滦电厂厂用电切换存在的问题及对策

稳定可靠的厂用电源对于电厂的安全稳定运行极其重要。介绍了厂用电切换方式,针对开滦电厂厂用电切换实际,探讨了在可行范围内解决其成功率不高的问题。     

铁路膨胀土路基工程病害与防治措施初探

我国膨胀土分布非常广泛,极易造成路基工程病害,若防治措施不当,对工程危害极大。结合西安南京铁路工程实践,从膨胀土路基出现的各类病害入手,根据膨胀土的工程特性及其病害产生的原因,提出了病害防治的措施及处理方法。     

浅谈桥面破损病害的成因及防治

简述了公路桥梁桥面破损病害的特征,分析了桥面破损的成因,提出了桥面破损的防治对策。     

铁路接头病害预防与整治探讨

结合工作中实际养护经验,分析了铁路接头产生病害的原因,在对接头病害原因进行分析的基础上,提出了防止铁路病害的措施与方法.     

海红果树锈病的发生与综合防治

就河曲县近年来海红果树锈病发生的危害、规律及防治技术进行了综述。     

Protective effect of sodium butyrate on the cell culture model of Huntington disease

This study aimed to develop a cell culture model of Huntington disease and observe the effect of sodium butyrate on this cell culture model. Exon 1 of both a wild type and a mutant IT15 gene from the genomic DNA of a healthy adult and a patient with Huntington disease was amplified and cloned into the eukaryotic expression vector pEGFP-C1. Human neuroblastoma SH-SY5Y cells were transiently transfected with these recombinant plasmids in the absence and presence of sodium butyrate (0.1, 0.2, 0.5, 1.0 mmol/L). The MTT assay was used to measure cell viability. The results indicated that the N-terminal fragment of mutant huntingtin formed perinuclear and intranuclear aggregates and caused a decrease of SH-SY5Y cell viability. Sodium butyrate inhibited the decrease of SH-SY5Y cell viability caused by the N-terminal fragment of mutant huntingtin. This suggests that sodium butyrate has a protective effect on this cell culture model of Huntington disease.