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61.
Robert J. Shmookler Reis Ramani Atluri Meenakshisundaram Balasubramaniam Jay Johnson Akshatha Ganne Srinivas Ayyadevara 《Aging cell》2021,20(5)
All neurodegenerative diseases feature aggregates, which usually contain disease‐specific diagnostic proteins; non‐protein constituents, however, have rarely been explored. Aggregates from SY5Y‐APPSw neuroblastoma, a cell model of familial Alzheimer''s disease, were crosslinked and sequences of linked peptides identified. We constructed a normalized “contactome” comprising 11 subnetworks, centered on 24 high‐connectivity hubs. Remarkably, all 24 are nucleic acid‐binding proteins. This led us to isolate and sequence RNA and DNA from Alzheimer''s and control aggregates. RNA fragments were mapped to the human genome by RNA‐seq and DNA by ChIP‐seq. Nearly all aggregate RNA sequences mapped to specific genes, whereas DNA fragments were predominantly intergenic. These nucleic acid mappings are all significantly nonrandom, making an artifactual origin extremely unlikely. RNA (mostly cytoplasmic) exceeded DNA (chiefly nuclear) by twofold to fivefold. RNA fragments recovered from AD tissue were ~1.5‐to 2.5‐fold more abundant than those recovered from control tissue, similar to the increase in protein. Aggregate abundances of specific RNA sequences were strikingly differential between cultured SY5Y‐APPSw glioblastoma cells expressing APOE3 vs. APOE4, consistent with APOE4 competition for E‐box/CLEAR motifs. We identified many G‐quadruplex and viral sequences within RNA and DNA of aggregates, suggesting that sequestration of viral genomes may have driven the evolution of disordered nucleic acid‐binding proteins. After RNA‐interference knockdown of the translational‐procession factor EEF2 to suppress translation in SY5Y‐APPSw cells, the RNA content of aggregates declined by >90%, while reducing protein content by only 30% and altering DNA content by ≤10%. This implies that cotranslational misfolding of nascent proteins may ensnare polysomes into aggregates, accounting for most of their RNA content. 相似文献
62.
Sinem Helvacıoğlu Mohammad Charehsaz Etil Güzelmeriç Mehmet Ali Oçkun İrem Ayran Hasan Kırmızıbekmez Yüksel Kan Ahmet Aydın Erdem Yeşilada 《化学与生物多样性》2021,18(10):e2000936
The antioxidant and mutagenic/antimutagenic activities of the fixed oils from Nigella sativa (NSO) and Nigella damascena (NDO) seeds, obtained by cold press-extraction from the cultivar samples, were comparatively investigated for the first time. The antimutagenicity test was carried out using classical and modified Ames tests. The fatty acid composition of the fixed oils was characterized by gas chromatography–mass spectrometry (GC-MS) while the quantification of thymoquinone in the fixed oils was determined by UPC2. The main components of the NSO and NDO were found to be linoleic acid, oleic acid, and palmitic acid. The results of the Ames test confirmed the safety of NSO and NDO from the viewpoint of mutagenicity. The results of the three antioxidant test methods were correlated with each other, indicating NDO as having a superior antioxidant activity, when compared to the NSO. Both NSO and NDO exhibited a significant protective effect against the mutagenicity induced by aflatoxin B1 in Salmonella typhimurium TA98 and TA100 strains. When microsomal metabolism was terminated after metabolic activation of the mycotoxin, a significant increase in antimutagenic activity was observed, suggesting that the degradation of aflatoxin B1 epoxides by these oils may be a possible antimutagenic mechanism. It is worthy to note that this is the first study to assess the mutagenicity of NSO and NDO according to the OECD 471 guideline and to investigate antimutagenicity of NDO in comparison to NSO against aflatoxin. 相似文献
63.
Dieu T. X. Nguyen Hung Tran Stefan Schwaiger Hermann Stuppner Stefania Marzocco 《化学与生物多样性》2021,18(1):e2000577
The extract of Elsholtzia ciliata aerial parts was subjected to bio-guided isolation using the intercellular ROS reduction in J774A.1 macrophages to monitor the anti-oxidative activity. Fifteen compounds were isolated from the active fractions including eleven flavonoids (vitexin, pedalin, luteolin-7-O-β-d -glucopyranoside, apigenin-5-O-β-d -glucopyranoside, apigenin-7-O-β-d -glucopyranoside, chrysoeriol-7-O-β-d -glucopyranoside, 7,3′-dimethoxyluteolin-6-O-β-d -glucopyranoside, luteolin, 5,6,4′-trihydroxy-7,3′-dimethoxyflavone, 5-hydroxy-6,7-dimethoxyflavone (compound 13 ), 5-hydroxy-7,8-dimethoxyflavone); three hydroxycinnamic acid derivatives (caffeic acid, 4-(E)-caffeoyl-l -threonic acid, 4-O-(E)-p-coumaroyl-l -threonic acid) and one fatty acid (α-linolenic acid). The biological evaluation of these compounds (10–2.5 μm ) indicated that all of them exerted good antioxidant and anti-inflammatory activities, in particular compound 13 . 相似文献
64.
65.
以春兰×寒香梅杂交种(Cymbidium goeringii×Cymbidium ‘Han Xiang Mei’)为材料,MS+琼脂4 g·L-1+蔗糖20 g·L-1+椰汁100 mL·L-1为基础培养基,通过单因素试验,探讨细胞分裂素(TDZ/6-BA)和无机盐浓度(P、K)对其试管花诱导的影响,测定花芽诱导的蛋白质、可溶性总糖含量与超氧化物歧化酶(SOD)活性及激素水平(IAA、ABA)。结果表明,添加0.2 mg·L-1 TDZ和2 mg·L-1 6-BA的花芽诱导率最高,分别为14.33%和14.00%;无机盐浓度3P/3K和3P/5K的培养基花芽诱导率较高,分别达16.67%和11.33%;花芽诱导最佳培养基为MS(3P, 3K)+TDZ 0.2 mg·L-1+椰汁100 mL·L-1+琼脂 4 g·L-1+蔗糖20 g·L-1,花芽诱导率可达34%左右。生理生化指标检测显示,可溶性蛋白、可溶性总糖含量及SOD活性与花芽诱导率呈正相关;稳定的内源激素IAA和ABA含量对花芽诱导有一定的积极作用,含量过高对花芽诱导有抑制作用。 相似文献
66.
以普通油茶(Camellia oleifera) 4个无性系为材料,结合油茶成花的动态观察和花芽分化过程的石蜡切片形态观察,采用酶联免疫吸附分析法测定花芽中玉米素核苷(ZR)、脱落酸(ABA)、生长素(IAA)、赤霉素(GA) 4种内源激素含量,探讨油茶花芽分化与内源激素的关系。油茶花芽分化过程可分为6个时期:前分化期(10 d)、萼片形成期(20 d)、花瓣形成期(30 d)、雌雄蕊形成期(20 d)、子房与花药形成期(10 d)和雌雄蕊成熟期(20 d),历时3~4个月。油茶不同无性系的花芽分化时间略有不同。油茶花芽中ZR含量相对较低(5.102~16.412 ng·g–1 FW),ABA含量相对较高(76.815~137.648 ng·g–1 FW)。其中,粤华5号和湘林8号的ZR、ABA含量变化趋势一致,岑软3号和岑软2号含量变化趋势一致。油茶花芽中IAA含量相对较高,为49.072~135.622 ng·g–1 FW,随着花芽分化进程,IAA含量均呈先升后降再升的变化趋势。GA含量相对较低,为5.616~13.720 ng·g–1 FW,随时间变化,呈现出不断降低的趋势。其中,不同无性系的IAA、GA含量变化趋势一致,而ZR、ABA含量变化趋势有所差异。ZR有利于花器官形成;高浓度IAA促进油茶花芽分化,低浓度IAA有利于开花;花芽中IAA与ABA存在明显的颉颃作用;GA抑制花芽分化。 相似文献
67.
Arthur Christopoulos Michael J. Lew 《Critical reviews in biochemistry and molecular biology》2013,48(5):359-391
AbstractAs we learn more about the biology of the Toll-like receptors (TLRs), a wide range of molecules that can activate this fascinating family of pattern recognition receptors emerges. In addition to conserved pathogenic components, endogenous danger signals created upon tissue damage are also sensed by TLRs. Detection of these types of stimuli results in TLR mediated inflammation that is vital to fight pathogenic invasion and drive tissue repair. Aberrant activation of TLRs by pathogenic and endogenous ligands has also been linked with the pathogenesis of an increasing number of infectious and autoimmune diseases, respectively. Most recently, allergen activation of TLRs has also been described, creating a third broad class of TLR stimulus that has helped to shed light on the pathogenesis of allergic disease. To date, microbial activation of TLRs remains best characterized. Each member of the TLR family senses a specific subset of pathogenic ligands, pathogen associated molecular patterns (PAMPS), and a wealth of structural and biochemical data continues to reveal the molecular mechanisms of TLR activation by PAMPs, and to demonstrate how receptor specificity is achieved. In contrast, the mechanisms by which endogenous molecules and allergens activate TLRs remain much more mysterious. Here, we provide an overview of our current knowledge of how very diverse stimuli activate the same TLRs and the structural basis of these modes of immunity. 相似文献
68.
《Free radical research》2013,47(8):990-1003
AbstractErythrocytes are continuously exposed to risk of oxidative injury due to oxidant oxygen species. To prevent damage, they have antioxidant agents namely, catalase (Cat), glutathione peroxidase (GPx), and peroxiredoxin 2 (Prx2). Our aim was to contribute to a better understanding of the interplay between Prx2, Cat, and GPx under H2O2-induced oxidative stress, by studying their changes in the red blood cell cytosol and membrane, in different conditions. These three enzymes were quantified by immunoblotting. Malondialdehyde, that is, lipoperoxidation (LPO) in the erythrocyte membrane, and membrane-bound hemoglobin (MBH) were evaluated, as markers of oxidative stress. We also studied the erythrocyte membrane protein profile, to estimate how oxidative stress affects the membrane protein structure. We showed that under increasing H2O2 concentrations, inhibition of the three enzymes with or without metHb formation lead to the binding of Prx2 and GPx (but not Cat) to the erythrocyte membrane. Prx2 was detected mainly in its oxidized form and the linkage of metHb to the membrane seems to compete with the binding of Prx2. Catalase played a major role in protecting erythrocytes from high exogenous flux of H2O2, since whenever Cat was active there were no significant changes in any of the studied parameters. When only Cat was inhibited, Prx2 and GPx were unable to prevent H2O2-induced oxidative stress resulting in increasing MBH and membrane LPO. Additionally, the inhibition of one or more of these enzymes induced changes in the anchor/linker proteins of the junctional complexes of the membrane cytoskeleton–lipid bilayer, which might lead to membrane destabilization. 相似文献
69.
Janne Leinonen Vappu Rantalaiho Terho Lehtimäki Timo Koivula Ole Wirta Amos Pasternack 《Free radical research》2013,47(4):273-281
Oxidative stress may be an important pathogenetic factor in the development of diabetic vascular complications. The total antioxidative potential of plasma reflects the ability of an individual to resist oxidative stress. We measured the plasma total peroxyl radical-trapping potential (TRAP) and the concentrations of four plasma chain-breaking antioxidants in 81 patients with non-insulin-dependent diabetes mellitus (NIDDM) nine years after diagnosis and in 102 well-matched non-diabetic control subjects. The association between the total antioxidative potential and the presence of coronary heart disease (CHD) and diabetic kidney disease were also studied. There were no significant differences in plasma TRAP between NIDDM patients and control subjects (1250 ± 199 vs. 1224 ± 198 μM). Nor were there any significant differences in the concentrations of plasma uric acid, ascorbic acid, α-tocopherol, and protein thiols between NIDDM patients and control subjects. Patients with a low glomerular filtration rate and/or high urinary albumin excretion had elevated plasma uric acid. Plasma TRAP was not, however, associated with renal dysfunction. The plasma of NIDDM patients with CHD had a significantly higher value of unidentified antioxidative potential than that of patients without CHD. This relation was strongly dependent upon smoking. In conclusion, these data demonstrate that there are no major defects in the antioxidative potential of plasma caused by NIDDM per se. CHD and diabetic renal dysfunction were not associated with changes in plasma TRAP. 相似文献
70.
R. Tyrrell 《Free radical research》2013,47(4):335-340
The ultraviolet A (UVA, 320–400 nm) component of sunlight has the potential to generate an oxidative stress in cells and tissue so that antioxidants (both endogenous and exogenous) strongly influence the biological effects of UVA. The expression of several genes (including heme oxygenase-1, HO-1; collagenase; the CL100 phosphatase and the nuclear oncogenes, c-fos and c-jun) is induced following physiological doses of UVA to cells and this effect can be strongly enhanced by removing intracellular glutathione or enhancing singlet oxygen lifetime. We have observed that heme is released from microsomal heme-containing proteins by UVA and other oxidants and that activation of HO-1 expression by UVA correlates with levels of heme release. UVA radiation also leads to an increase in labile iron pools (either directly or via HO-1) and eventual increases in ferritin levels. The role of heme oxygenase in protection of skin fibroblasts is probably an emergency inducible defense pathway to remove heme liberated by oxidants. The slower increase in ferritin levels is an adaptive response which serves to keep labile iron pools low and thereby reduce Fenton chemistry and oxidant-induced chain reactions involving lipid peroxidation. In keratinocytes, the primary target of UVA radiation, heme oxygenase levels are constitutively high (because of HO-2 expression). Since there is a corresponding increase in basal levels of ferritin the epidermis appears to be well protected constitutively against the oxidative stress generated by UVA. 相似文献