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91.
Tao Ke Filipe Marques Gonçalves Cinara Ludvig Gonçalves Alessandra Antunes dos Santos João B.T. Rocha Marcelo Farina Anatoly Skalny Aristidis Tsatsakis Aaron B. Bowman Michael Aschner 《生物化学与生物物理学报:疾病的分子基础》2019,1865(8):2068-2081
Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity. 相似文献
92.
Smad4, originally isolated from the human chromosome 18q21, is a key factor in transducing the signals of the TGF-β superfamily of growth hormones and plays a pivotal role in mediating antimitogenic and proapoptotic effects of TGF-β, but the mechanisms by which Smad4 induces apoptosis are elusive. Here we report that Smad4 directly translocates to the mitochondria of apoptotic cells. Smad4 gene silencing by siRNA inhibits TGF-β-induced apoptosis in Hep3B cells and UV-induced apoptosis in PANC-1 cells. Cell fractionation assays demonstrated that a fraction of Smad4 translocates to mitochondria after long time TGF-β treatment or UV exposure, during which the cells were under apoptosis. Smad4 mitochondria translocation during apoptosis was also confirmed by fluorescence observation of Smad4 colocalization with MitoTracker Red. We searched for mitochondria proteins that have physical interactions with Smad4 using yeast two-hybrid screening approach. DNA sequence analysis identified 34 positive clones, five of which encoded subunits in mitochondria complex IV, i.e., one clone encoded cytochrome c oxidase COXII, three clones encoded COXIII and one clone encoded COXVb. Strong interaction between Smad4 with COXII, an important apoptosis regulator, was verified in yeast by β-gal activity assays and in mammalian cells by immunoprecipitation assays. Further, mitochondrial portion of cells was isolated and the interaction between COXII and Smad4 in mitochondria upon TGF-β treatment or UV exposure was confirmed. Importantly, targeting Smad4 to mitochondria using import leader fusions enhanced TGF-β-induced apoptosis. Collectively, the results suggest that Smad4 promote apoptosis of the cells through its mitochondrial translocation and association with mitochondria protein COXII. 相似文献
93.
茶叶上拟除虫菊酯类农药降解菌的分离及其特性 总被引:17,自引:0,他引:17
生物修复对降解污染基质中的农药是一种对环境有益的方法。目标是要寻找能够降解在茶叶生产中使用的拟除虫菊酯类农药的降解菌。最终在福州某茶园经农药处理过的茶叶中分离降解菌。首先在富集培养基中筛选,接着在以农药为唯一碳源的基础培养基中连续筛选。结果发现,其中一株标号为c1f6的菌株生长的特别良好,经AMS-VITEK120全自动微生物分析系统鉴定,为假单胞菌属的一个未知种。采用HP6890气相色谱仪测定菌株对拟除虫菊酯类农药联苯菊酯、甲氰菊酯和氯氰菊酯的降解率。在pH7.0的基础培养基发酵液中,以各加100mg·L-1这3种农药为唯一碳源,30℃振荡培养,接种c1f6后3d,这3种农药的降解率分别为55.64%、44.56%和52.19%。采用光密度测定的菌株生长值和农药降解率的关系曲线表明,在基础培养基中,农药降解和菌株生长成正相关,说明菌株能以拟除虫菊酯类农药为唯一碳源和能源进行生长。采用同样的方法测定表明,菌株c1f6对有机磷农药也有一定的降解力,3d对甲胺磷和毒死蜱的降解率分别为27.67%和12.35%。因此,假单胞菌c1f6是一株较广谱的农药降解菌,有望用于生物修复过程,以减少茶叶栽培过程中的产品和环境污染。 相似文献
94.
We propose that the unique temperature dependence of the Chance-De Vault cytochrome oxidation reaction in Chromatium is not due to a transition from low-temperature nuclear tunnelling to a high-temperature activated electron transfer (ET), but rather originates from two parallel ET processes from two distinct low-potential cytochromes to the bacteriochlorophyll dimer cation. These involve a slow activationless process, which dominates at low temperatures (T 120 K) and an activated process, which is practically exclusive at high temperatures. This conjecture provides plausible nuclear and electronic coupling terms and structural data for the two cytochrome oxidation reactions. 相似文献
95.
Hanna G. Budayeva Arundhati Sengupta-Ghosh Lilian Phu John G. Moffat Gai Ayalon Donald S. Kirkpatrick 《Molecular & cellular proteomics : MCP》2022,21(4):100221
Muscle-specific receptor tyrosine kinase (MuSK) agonist antibodies were developed 2 decades ago to explore the benefits of receptor activation at the neuromuscular junction. Unlike agrin, the endogenous agonist of MuSK, agonist antibodies function independently of its coreceptor low-density lipoprotein receptor–related protein 4 to delay the onset of muscle denervation in mouse models of ALS. Here, we performed dose–response and time-course experiments on myotubes to systematically compare site-specific phosphorylation downstream of each agonist. Remarkably, both agonists elicited similar intracellular responses at known and newly identified MuSK signaling components. Among these was inducible tyrosine phosphorylation of multiple Rab GTPases that was blocked by MuSK inhibition. Importantly, mutation of this site in Rab10 disrupts association with its effector proteins, molecule interacting with CasL 1/3. Together, these data provide in-depth characterization of MuSK signaling, describe two novel MuSK inhibitors, and expose phosphorylation of Rab GTPases downstream of receptor tyrosine kinase activation in myotubes. 相似文献
96.
E2F6在物理性低氧及化学性低氧诱导的凋亡中的表达特征 总被引:6,自引:0,他引:6
心肌细胞凋亡性死亡是低氧发生时的重要病理学特征,但低氧诱导的心肌细胞凋亡的调控机制尚未完全阐明.E2F6是E2F转录因子家族成员之一,我们新近的研究证实其具有抑制DNA损伤诱导的细胞凋亡作用.但是,E2F6是否参与了低氧诱导的心肌细胞凋亡的调控尚不清楚.在本研究中,我们初步探讨了E2F6在物理性低氧及化学性低氧模拟物诱导大鼠心肌细胞系H9c2细胞凋亡中的表达特征.结果表明:物理性低氧、化学性低氧模拟物去铁胺(desferrioxamine,DFO)和氯化钻(cobalt chloride,CoCl2)均能有效诱导H9c2细胞发生凋亡.在物理性低氧及CoCl2,诱导的H9c2细胞凋亡中,内源性E2F6 mRNA表达明显下调,但蛋白表达没有明显变化.而在DFO诱导的凋亡中,内源性E2F6 mRNA及蛋白表达均发生明显下调.这些结果提示,E2F6可能参与调控DFO模拟低氧诱导的H9c2细胞凋亡,而对物理性低氧及CoCl2,模拟低氧诱导的细胞凋亡敏感性较低.此外,DFO模拟低氧诱导的细胞凋亡机制可能与物理性低氧及CoCl2.模拟低氧诱导的细胞凋亡机制不同. 相似文献
97.
It was observed that during fermentative production of recombinant ovine interferon-tau (r-oIFN-tau) in Pichia pastoris, a secreted recombinant protein, the protein was degraded increasingly after 48 h of induction and the rate of degradation increased towards the end of fermentation at 72 h, when the fermentation was stopped. Proteases, whose primary source was the vacuoles, was found in increasing levels in the cytoplasm and in the fermentation broth after 48 h of induction and reached maximal values when the batch was completed at 72 h. Protease levels at various cell fractions as well as in the culture supernatant were lower when glycerol was used as the carbon source instead of methanol. It can be concluded that methanol metabolism along with cell lysis towards the end of fermentation contributes to increased proteolytic activity and eventual degradation of recombinant protein. 相似文献
98.
目的:研究一株自制的c-erbB-2单克隆抗体A18在乳腺癌中表达的特性。方法:应用免疫组织化学SP法、蛋白质印迹分析法和荧光激活的流式细胞分选检测技术检测A18在635例乳腺癌组织、100例癌旁乳腺组织、不表达c-erbB-2的NIH/3T3(鼠成纤维细胞)和NE91(转表皮生长因子受体基因的NR6鼠成纤维面积)细胞株及高表达c-erbB-2的T6-17(转c-erbB-2-基因的NIH/3T3细胞)和SKBR3(人乳腺癌细胞)细胞株中的表达状况,并与市售进口c-erbB-2抗体(MaximBiotech产品)进行了平行对照研究。A18系采用细胞表面区域表位包埋法免疫小鼠制备而成,,结果:A18阳性染色定位于细胞膜,部分伴微弱的细胞浆着色,无明显非特异性染色,A18和进口抗体对NIH/3T3、NE91细胞均呈阴性,T6-17、SKBR3细胞均呈阳性,在乳腺癌组织中,A18的阳性率为60.3%,明显高于癌旁乳腺组织的5.0%,A18与进口同类单抗的阴性、阳性及总符合率分别为84.0%、82.8%及83.2%,与进口同类多抗的阴性,阳性及总符合率分别为88.0%、90.2%和89.5%。A1和进口同类单抗与乳腺癌临床病理特征的关系一致。经反复冻融7次或4℃保存10个月A18效价仍保持在3μg/ml。结论:A18特异性强,定位准确,效价高而稳定、可用于临床乳腺癌的检测。 相似文献
99.
Edward Málaga-Trillo Evgenia Salta Antonio FiguerasCynthia Panagiotidis Theodoros Sklaviadis 《生物化学与生物物理学报:疾病的分子基础》2011,1812(3):402-414
Transmissible spongiform encephalopathies (TSEs), otherwise known as prion disorders, are fatal diseases causing neurodegeneration in a wide range of mammalian hosts, including humans. The causative agents - prions - are thought to be composed of a rogue isoform of the endogenous prion protein (PrP). Beyond these and other basic concepts, fundamental questions in prion biology remain unanswered, such as the physiological function of PrP, the molecular mechanisms underlying prion pathogenesis, and the origin of prions. To date, the occurrence of TSEs in lower vertebrates like fish and birds has received only limited attention, despite the fact that these animals possess bona fide PrPs. Recent findings, however, have brought fish before the footlights of prion research. Fish models are beginning to provide useful insights into the roles of PrP in health and disease, as well as the potential risk of prion transmission between fish and mammals. Although still in its infancy, the use of fish models in TSE research could significantly improve our basic understanding of prion diseases, and also help anticipate risks to public health. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases. 相似文献
100.
Biochemical characterization of a chromosomal toxin-antitoxin system in Mycobacterium tuberculosis 总被引:1,自引:0,他引:1
In the present paper, we report the biochemical characterization of a chromosomal toxin-antitoxin (TA) system in Mycobacterium tuberculosis, consisting of the Rv1991c gene and its upstream open reading frame (ORF) termed Rv1991a. Rv1991c was characterized as a toxin with ribonuclease activity and Rv1991a as the antitoxin against Rv1991c. Rv1991a interacted with Rv1991c to form a complex. A promoter located immediately upstream of Rv1991a was identified. Both Rv1991a and the Rv1991a-Rv1991c complex were able to bind to the promoter region of the Rv1991a-Rv1991c operon, indicating that the expression of the Rv1991a-Rv1991c operon can be autoregulated. 相似文献