泛素–蛋白酶体系统在铁死亡中的作用

铁死亡是一种新型的由铁积累和脂质过氧化驱动的调节性细胞死亡方式,且越来越多的证据表明铁死亡对包括肿瘤在内的多种疾病的发生发展有重要作用。因此,利用铁死亡进行疾病的治疗也成为基础研究和临床研究的一大方向。泛素–蛋白酶体系统(the ubiquitin-proteasome system,UPS)是真核生物蛋白的主要降解途径之一,是由泛素(ubiquitin,Ub)先标记要降解的蛋白质,进而由蛋白酶体识别和降解的过程。泛素–蛋白酶体途径功能失调会导致多种病理过程发生,因此,它对维持生物体机能稳定具有重要的意义。蛋白质稳定性的调节是铁死亡复杂的分子机制中至关重要的一部分,而泛素–蛋白酶体系统作为真核生物中大分子稳态的关键调节系统,它可以通过调节铁死亡相关分子或相关信号通路等多种方式直接或间接影响铁死亡,在铁死亡中发挥着重要作用。因此,该文就泛素–蛋白酶体系统参与调节铁死亡的相关分子或信号通路等方面进行综述,以期为以铁死亡为靶点的疾病治疗提供一定参考。

泛素化途径在奶牛乳脂生成过程中的调控作用

泛素化途径是真核细胞中主要的蛋白质降解途径,其中泛素–蛋白酶体途径主要降解细胞质中的蛋白,溶酶体途径主要降解细胞膜蛋白。研究表明,泛素化途径在奶牛乳腺上皮细胞脂肪酸合成过程中起着关键的调控作用。在脂肪酸摄取过程中,泛素化途径调控异常可导致细胞膜上脂肪酸转运蛋白的泛素化降解受阻,使脂肪酸转运增强,进而增加奶牛乳脂的生成。本文综述了泛素化途径在奶牛乳脂生成过程中对相关蛋白的调控作用,以期为奶牛乳脂性状后续相关研究提供参考和新的思路。

PSMD2在肿瘤中的研究进展

泛素蛋白酶体途径(Alterations in the ubiquitin-proteasome system UPS),是由泛素介导的一种高度复杂的蛋白降解系统,普遍参与各种生物学功能,例如细胞生长,细胞周期进程,DNA转录、损伤、修复和信号转导及自噬,因此在体内各种调节蛋白的降解和整体细胞的稳态中发挥着至关重要的作用。UPS的表达功能异常或改变可能导致蛋白质的积累,与人类多种疾病相关,包括恶性肿瘤、血液系统疾病等。其中泛素化是泛素蛋白酶体系统途径的关键步骤,PSMD2 (proteasome 26S subunit, non-ATPase 14)位于蛋白酶体26S亚基,是一种非ATP酶组分,是泛素–蛋白酶体的重要组成部分之一。近年来,其在疾病发生发展中的作用越来越受到关注,本文将对PSMD2的结构、作用机制及在不同疾病中的研究进展进行综述。

肿瘤恶病质骨骼肌消耗机制的研究进展

目的:从泛素–蛋白酶体系统(UPS)与自噬–溶酶体系统(ALS)探讨肿瘤恶病质骨骼肌消耗的机制及其上游信号通路,从而为恶病质发生的防治研究提供依据。方法:检索Medline相关文献,以“肿瘤恶病质、骨骼肌消耗”等为关键词,检索1971-01~2013-06的相关文献,共检索到英文文献898条。纳入标准:1) 近10年相关文献;2) 与骨骼肌消耗的信号通路及效应因子相关。剔除标准1) 与肿瘤恶病质无关的骨骼肌消耗;2) 与UPS或ALS无关的信号通路及效应因子。符合纳入标准的英文文献87条,根据剔除标准剔除英文文献31条,最后纳入分析25篇文献。结果:在肿瘤恶病质的发生发展过程中,多种效应因子通过调节UPS与ALS两大系统的作用,促进了蛋白质的降解,进而造成骨骼肌的消耗。结论:UPS与ALS为参与肿瘤恶病质骨骼肌消耗的两大重要系统,如果可以阻断造成UPS与ALS两大系统交互作用异常放大的通路,肿瘤恶病质的发生就能够得以控制,进而改善肿瘤患者的生存质量、延长其生存期,甚至为肿瘤患者的康复带来一线希望。

UBR5在肿瘤发生发展中作用及其机制研究进展

泛素蛋白酶系统(ubiquitin-proteasome system, UPS)是细胞信号转导和蛋白质稳定的重要调节因子,对多种细胞过程有着重要的作用。泛素蛋白链接酶E3识别素5,(ubiquitin protein ligase E3 component n-recognin 5, UBR5,又名EDD1)具有独特的结构特征,参与了DNA损伤反应、代谢、转录和凋亡的调节,在癌症和发育过程中成为UPS的关键调节因子。UBR5在癌症中的作用引起了科研人员的广泛关注。本文将从UBR5的结构、泛素化与E3泛素化连接酶的作用、UBR5在各种癌症中的作用及其作用机制进行综述。

Nuclear effects of ethanol-induced proteasome inhibition in liver cells

Alcohol ingestion causes alteration in several cellular mechanisms, and leads to inflammation, apoptosis, immunological response defects, and fibrosis. These phenomena are associated with significant changes in the epigenetic mechanisms, and subsequently, to liver cell memory. The ubiquitin-proteasome pathway is one of the vital pathways in the cell that becomes dysfunctionial as a result of chronic ethanol consumption. Inhibition of the proteasome activity in the nucleus causes changes in the turnover of transcriptional factors, histone modifying enzymes, and therefore, affects epigenetic mechanisms. Alcohol consumption has been associated with an increase in histone acetylation and a decrease in histone methylation, which leads to gene expression changes. DNA and histone modifications that result from ethanol-induced proteasome inhibition are key players in regulating gene expression, especially genes involved in the cell cycle, immunological responses, and metabolism of ethanol. The present review highlights the consequences of ethanol-induced proteasome inhibition in the nucleus of liver cells that are chronically exposed to ethanol.

Effect of acupuncture in intervening heroin-induced brain damage via regulating ubiquitin-proteasome pathway

Objective：To observe the effect of acupuncture in regulating ubiquitin-proteasome pathway （UPP）,and discuss the action of acupuncture in intervening heroin-induced brain damage.Methods：Thirty male Sprague-Dawley （SD） rats were divided into a control group,a model group and an acupuncture group by using the random number table.Rats in the model and acupuncture groups received intramuscular heroin injection for successive 8 d at a progressively increased dose.Afterwards,the injection was suspended for 5 d for withdrawal.The heroin relapse rat model was established by repeating the drug addiction and withdrawal process for 3 times.The control group followed the step of the model establishment,but was given intramuscular injection of normal saline at the stage of addiction and no intervention at the stage of withdrawal;the model group was given intramuscular heroin injection at a progressively increased dose at the addiction stage and no intervention at the withdrawal stage;the acupuncture group was dealt in the same way as the model group at the addiction stage,but received acupuncture at Baihui （GV 20） and Dazhui （GV 14） at the withdrawal stage,with the needles retained for 30 min each time,1 session a day,for successive 5 d.On the 39th day,brain tissues were extracted from the hippocampus and ventral tegmental area （VTA） of the three groups of rats.The apoptosis of brain nerve cells was detected by using terminal deoxynucleotidyl transferase-mediated nick and labeling （TUNEL）.The mRNA and protein expressions of ubiquitin （Ub）,ubiquitin protein ligase （E3） and 26S were examined by immunohistochemistry and quantitative real-time polymerase chain reaction （RT-qPCR）.Results：Compared with the model group,rat＇s hippocampus and VTA in the acupuncture group showed significantly fewer cells positively stained by TUNEL staining （P〈0.01）,and its mRNA and protein expressions of Ub,E3,26S were significantly lower （P〈0.01）.Conclusion：Reducing nerve cell apoptosis and regulating the mRNA and protein expressions of Ub,E3 and 26S in rat＇s hippocampus and VTA are possibly one of the action mechanisms of acupuncture in intervening heroin-induced brain damage.