Protein glycation

蛋白质糖基化
  • 文章类型: Journal Article
    干燥条件显著影响多糖的组成和微观结构,对它们的化学特性和生物活性产生各种影响。这项研究的目的是调查不同的工业干燥技术,即,热风干燥,红外干燥,微波真空干燥,和冷冻干燥,影响刺梨果实多糖(RRTP)的结构特性和生物活性。结果表明,这些干燥方法显着改变了提取率,分子量,单糖比例,糖醛酸和总糖的含量,胶凝特性,颗粒大小,热稳定性,和RRTPs的微观结构。然而,多糖的单糖组成和官能团在不同的干燥技术中保持一致。生物活性分析表明,RRTPs,特别是通过微波真空干燥(MVD-RRTP)处理的那些,表现出优异的抗亚油酸氧化,强大的抗糖基化作用,和显著的体外抑制α-葡萄糖苷酶。这项研究的结果表明,微波真空干燥作为RRTPs有效的预提取干燥方法,增强其生物活性。该技术特别有利于制备用于功能性食品和药物的RTPs。为工业应用优化其促进健康的特性。
    Drying conditions significantly impact the compositions and microstructures of polysaccharides, leading to various effects on their chemical characteristics and bioactivities. The objective of this study was to investigate how different industrial drying techniques, i.e., hot air drying, infrared drying, microwave vacuum drying, and freeze drying, affect the structural properties and biological activities of polysaccharides extracted from Rosa roxburghii Tratt fruit (RRTP). Results revealed that these drying methods significantly altered the extraction yield, molecular weights, monosaccharide ratios, contents of uronic acid and total sugars, gelling properties, particle sizes, thermal stability, and microstructures of RRTPs. However, the monosaccharide composition and functional groups of polysaccharides remained consistent across the different drying techniques. Biological activity assays demonstrated that RRTPs, particularly those processed through microwave vacuum drying (MVD-RRTP), exhibited excellent anti-linoleic acid oxidation, robust anti-glycosylation effects, and significant α-glucosidase inhibition in vitro. The outcomes of this research demonstrate that microwave vacuum drying serves as an effective pre-extraction drying method for RRTPs, enhancing their biological activities. This technique is particularly advantageous for preparing RRTPs intended for use in functional foods and pharmaceuticals, optimizing their health-promoting properties for industrial applications.
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  • 文章类型: Journal Article
    通过使用纳米颗粒(NPs)增强种子萌发具有引发具有重要生物医学应用的更多所需化合物的合成的潜力。例如防止蛋白质糖基化,发生在糖尿病中。这里,我们使用7nm和100nm的ZnO和4.5nm和16.7nm的Fe2O3NP处理向日葵种子。我们评估了对发芽的影响,总酚含量,和提取的多酚的抗糖基化潜力。在不同浓度的NP溶液中浸泡后,使向日葵种子在体外发芽。多酚被提取,剂量,用于血清白蛋白糖化实验。100nm的ZnONPs显着提高了种子的发芽速度,而4.5nm的Fe2O3NPs显着降低了种子的发芽速度。种子总酚含量(TPC)受NP类型的影响,随着ZnONPs增强TPC,和NPs的大小,较小的NP导致参数的改善。从种子中提取的多酚抑制蛋白质糖基化,特别是从用7nmZnO处理的种子中提取的。NPs的使用影响向日葵种子的发芽速度和总多酚含量,强调NP类型和大小在发芽过程中的重要性。
    The enhancement of seed germination by using nanoparticles (NPs) holds the potential to elicit the synthesis of more desired compounds with important biomedical applications, such as preventing protein glycation, which occurs in diabetes. Here, we used 7 nm and 100 nm ZnO and 4.5 nm and 16.7 nm Fe2O3 NPs to treat sunflower seeds. We evaluated the effects on germination, total phenolic content, and the anti-glycation potential of extracted polyphenols. Sunflower seeds were allowed to germinate in vitro after soaking in NP solutions of different concentrations. Polyphenols were extracted, dosed, and used in serum albumin glycation experiments. The germination speed of seeds was significantly increased by the 100 nm ZnO NPs and significantly decreased by the 4.5 nm Fe2O3 NPs. The total phenolic content (TPC) of seeds was influenced by the type of NP, as ZnO NPs enhanced TPC, and the size of the NPs, as smaller NPs led to improved parameters. The polyphenols extracted from seeds inhibited protein glycation, especially those extracted from seeds treated with 7 nm ZnO. The usage of NPs impacted the germination speed and total polyphenol content of sunflower seeds, highlighting the importance of NP type and size in the germination process.
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  • 文章类型: Journal Article
    晚期糖基化终产物(AGEs)通过碳水化合物与生物大分子的非酶促连接形成。这些AGEs与它们的同源受体结合,称为AGEs受体(RAGEs),成为几种疾病发生和发展的重要原因之一。深入了解RAGE的途径将有助于确定新的干预方式作为新治疗策略的一部分。尽管存在几种使用小分子靶向该途径的方法,植物来源的化合物等,纳米粒子已被证明是一种关键的方法,考虑到它的几个优点。高生物利用度,生物相容性,穿越血脑屏障的能力和可修饰的表面特性使纳米粒子比其他策略更具优势。在这一章中,我们将讨论AGEs,它们参与疾病和用于靶向该途径的纳米颗粒。
    Advanced glycation end products (AGEs) are formed by the non-enzymatic attachment of carbohydrates to a biological macromolecule. These AGEs bind to their cognate receptor called receptor for AGEs (RAGEs), which becomes one of the important causal factors for the initiation and progression of several diseases. A deep understanding into the pathways of RAGEs will help in identifying novel intervention modalities as a part of new therapeutic strategies. Although several approaches exist to target this pathway using small molecules, compounds of plant origin etc, nanoparticles have proven to be a critical method, given its several advantages. A high bioavailability, biocompatibility, ability to cross blood brain barrier and modifiable surface properties give nanoparticles an upper edge over other strategies. In this chapter, we will discuss AGEs, their involvement in diseases and the nanoparticles used for targeting this pathway.
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  • 文章类型: Journal Article
    在糖尿病血糖水平升高的情况下,蛋白质的非酶糖基化加速。维生素和矿物质缺乏与糖尿病的发病和进展密切相关。各种水溶性和脂溶性维生素的抗糖基化能力,以及钼(Mo)等微量矿物质,锰(Mn),镁(Mg),铬,等。,已经使用牛血清白蛋白(BSA)作为体外模型进行了筛选。BSA与甲基乙二醛(MGO)在37°C下孵育48小时,与矿物质和维生素分开,以及对照和氨基胍(AG)作为比较矿物质和维生素功效的标准。Further,检查了它们对肾细胞(HEK-293)抗氧化潜力的影响。通过监测蛋白质糖基化标志物来测量抗糖基化潜力,结构和功能修改。一些矿物质,Mo,Mn,Mg,在最大生理浓度下,对蛋白质结合的羰基含量和β-淀粉样蛋白聚集的抑制作用相当。Mo和Mg保护了巯基和游离氨基酸,并保留了抗氧化潜力。维生素E,D,B1和B3显示显著的糖化抑制和改善的抗氧化潜力在HEK-293细胞通过评估脂质过氧化评估,SOD和乙二醛酶活性。这些结果强调了维生素和矿物质的糖化抑制潜力,表明这些微量营养素在糖尿病管理治疗前景中的应用前景。
    Nonenzymatic glycation of proteins is accelerated in the context of elevated blood sugar levels in diabetes. Vitamin and mineral deficiencies are strongly linked to the onset and progression of diabetes. The antiglycation ability of various water- and fat-soluble vitamins, along with trace minerals like molybdenum (Mo), manganese (Mn), magnesium (Mg), chromium, etc., have been screened using Bovine Serum Albumin (BSA) as in vitro model. BSA was incubated with methylglyoxal (MGO) at 37 °C for 48 h, along with minerals and vitamins separately, along with controls and aminoguanidine (AG) as a standard to compare the efficacy of the minerals and vitamins. Further, their effects on renal cells\' (HEK-293) antioxidant potential were examined. Antiglycation potential is measured by monitoring protein glycation markers, structural and functional modifications. Some minerals, Mo, Mn, and Mg, demonstrated comparable inhibition of protein-bound carbonyl content and ß-amyloid aggregation at maximal physiological concentrations. Mo and Mg protected the thiol group and free amino acids and preserved the antioxidant potential. Vitamin E, D, B1 and B3 revealed significant glycation inhibition and improved antioxidant potential in HEK-293 cells as assessed by estimating lipid peroxidation, SOD and glyoxalase activity. These results emphasize the glycation inhibitory potential of vitamins and minerals, indicating the use of these micronutrients in the prospect of the therapeutic outlook for diabetes management.
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  • 文章类型: Journal Article
    这项研究深入研究了由8%和72%阿洛酮糖组成的高固体明胶-糖类混合物中的美拉德反应(MR),果糖,或者低聚果糖,在凝胶化之前进行不同持续时间(0-60min)的热处理。凝胶的物理化学性质,包括颜色,化学成分,蛋白质交联,机械强度,体外消化率和抗氧化活性,被表征。在pH~5.5和中等水分活度(0.6-0.7)时,通过糖降解和糖胺相互作用观察到快速褐变,长时间加热加剧了这种情况。糖类的MR反应性如下:AL>FRU>FOS。特色产品(MRP,例如,α-二羰基,5-羟甲基糠醛,和晚期糖基化终产物)被鉴定,MRP的光谱在单糖和寡糖之间显著不同。MR诱导的蛋白质糖基化和交联对凝胶强度和体外蛋白质消化率表现出一定的负面影响。此外,所有明胶-糖类混合物表现出增强的抗氧化性能,明胶-AL混合物显示最高的自由基清除率。
    This research delves into the Maillard reaction (MR) in high-solid gelatin-saccharide mixtures consisting of 8% and 72% of allulose, fructose, or fructo-oligosaccharides, which were subjected to varied duration (0-60min) of thermal processing prior to gelation. Physicochemical properties of the gels, including color, chemical composition, protein crosslinking, mechanical strength, in-vitro digestibility and antioxidant activities, were characterized. At pH ∼5.5 and intermediate water activities (0.6-0.7), fast browning was observed through sugar degradation and sugar-amine interactions, which were intensified by prolonged heating. The MR reactivity of saccharides followed: AL > FRU > FOS. Characteristic products (MRPs, e.g., α-dicarbonyls, 5-hydroxymethylfurfural, and advanced glycation end products) were identified, with the spectra of MRPs varying significantly between monosaccharides and oligosaccharides. The MR-induced protein glycation and crosslinking exhibited certain negative impacts on the gel strength and in-vitro protein digestibility. Furthermore, all gelatin-saccharide mixtures exhibited augmented antioxidant properties, with the gelatin-AL mixtures displaying the highest free radical scavenging rates.
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  • 文章类型: Journal Article
    众所周知,患有高血糖症的人具有较高的发展帕金森病(PD)的倾向。将这两种病理联系起来的最合理的机制之一是神经元蛋白的糖基化及其病理后果。α-突触核蛋白,PD的一个关键组成部分,可以在其15个赖氨酸处糖化。事实上,已在从体内分离的聚集的α-突触核蛋白上检测到该过程的终产物。然而,糖基化的后果并不完全清楚,这对于理解糖尿病与PD之间联系的潜在机制至关重要。为了更好地澄清这一点,我们在这里研究了甲基乙二醛(细胞质中最重要的羰基化合物)如何影响α-突触核蛋白的构象和聚集倾向,以及它聚集和融合突触状囊泡的能力。获得的数据证明甲基乙二醛通过形成MOLD诱导Lys-Lys交联。然而,这对α-突触核蛋白的平均构象集合没有显着影响,尽管它完全耗尽了其形成可溶性寡聚体和不溶性淀粉样原纤维的天然倾向。此外,甲基乙二醛对α-突触核蛋白的结合能力有破坏作用,簇和融合突触状囊泡。
    It is well-known that people suffering from hyperglycemia have a higher propensity to develop Parkinson\'s disease (PD). One of the most plausible mechanisms linking these two pathologies is the glycation of neuronal proteins and the pathological consequences of it. α-Synuclein, a key component in PD, can be glycated at its fifteen lysine. In fact, the end products of this process have been detected on aggregated α-synuclein isolated from in vivo. However, the consequences of glycation are not entirely clear, which are of crucial importance to understand the mechanism underlying the connection between diabetes and PD. To better clarify this, we have here examined how methylglyoxal (the most important carbonyl compound found in the cytoplasm) affects the conformation and aggregation propensity of α-synuclein, as well as its ability to cluster and fuse synaptic-like vesicles. The obtained data prove that methylglyoxal induces the Lys-Lys crosslinking through the formation of MOLD. However, this does not have a remarkable effect on the averaged conformational ensemble of α-synuclein, although it completely depletes its native propensity to form soluble oligomers and insoluble amyloid fibrils. Moreover, methylglyoxal has a disrupting effect on the ability of α-synuclein to bind, cluster and fusion synaptic-like vesicles.
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  • 文章类型: Journal Article
    晚期糖基化终产物(AGEs)可在糖氧化反应期间引起。这种反应与糖尿病并发症和健康问题的后果有关。因此,我们正在探索高地大麦蛋白水解物(HBPHs)对AGE形成的禁止作用。在这里,首先在各种pH条件下从高原大麦中提取蛋白质,然后使用四种不同的蛋白水解酶(flavourzyme,胰蛋白酶,木瓜蛋白酶,胃蛋白酶)在不同程度的水解。我们评估了三度水解产物(最低,中间,最高)用于表征抗氧化活性和理化性质的酶。在所有的水解产物中,黄酮酶处理的水解产物F-1,F-2和F-3表明清除DPPH的能力很高(IC50值为0.97%,0.63%,和0.90%),结构和功能特性。最后,在多个葡萄糖-糖化牛血清白蛋白(BSA)系统中评估了活性最强的水解产物F-1,F-2和F-3对AGEs形成的抑制作用.此外,在BSA系统中,F-3表现出较强的抗糖基化活性,有效抑制非荧光AGE(CML),和果糖胺水平。此外,它减少了羰基化合物,同时也防止了硫醇基团的损失。我们的结果将有益于食品工业作为几种慢性疾病的潜在抗糖基化剂的应用。
    Advanced glycation end products (AGEs) can be caused during a glycoxidation reaction. This reaction is associated with complications of diabetes and the consequences of health problems. Therefore, we are exploring the prohibitory effect of highland barley protein hydrolysates (HBPHs) on AGE formation. Herein, first extracted the protein from highland barley with various pH conditions and then hydrolyzed using four different proteolytic enzymes (flavourzyme, trypsin, papain, pepsin) under different degrees of hydrolysis. We assessed three degrees of hydrolysates (lowest, middle, highest) of enzymes used to characterize the antioxidant activity and physicochemical properties. Among all the hydrolysates, flavourzyme-treated hydrolysates F-1, F-2, and F-3 indicated the high ability to scavenge DPPH (IC50 values of 0.97 %, 0.63 %, and 0.90 %), structural and functional properties. Finally, the inhibitory effect of the most active hydrolysates F-1, F-2, and F-3 against the AGEs formation was evaluated in multiple glucose-glycated bovine serum albumin (BSA) systems. Additionally, in a BSA system, F-3 exhibited the strong antiglycation activity, effectively suppressed the non-fluorescent AGE (CML), and the fructosamine level. Moreover, it decreased carbonyl compounds while also preventing the loss of thiol groups. Our results would be beneficial in the application of the food industry as a potential antiglycation agent for several chronic diseases.
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  • 文章类型: Journal Article
    目的:我们先前显示了L-赖氨酸(Lys)的有益作用,一个化学伴侣,减轻糖尿病大鼠和2型糖尿病患者的糖尿病并发症。在这里,我们评估了Lys与维生素C和锌(Lys+VC+Zn)联合给药的效果,在糖尿病大鼠中。
    方法:将链脲佐菌素(50mg/Kg)注射到雄性成年Wistar大鼠中,以诱发糖尿病。然后,正常和糖尿病大鼠分别用Lys和LysVCZn治疗5个月。所以,两组的饮用水中均有0.1%的Lys。对照组仅接受水。在实验过程中,体重,并在血液中确定了各种参数,血清/血浆,和老鼠的尿液。
    结果:生化指标的测定证实了大鼠糖尿病的诱发及其并发症。Lys或Lys+VC+Zn治疗导致血糖和蛋白质糖基化降低(AGEs和HbA1c降低),胰岛素分泌增加,减轻胰岛素抵抗和HOMA-IR,改善血脂和HDL功能(LCAT和PON1),增强的抗氧化剂状态(FRAP和AOPP),改善肾功能(减少微量白蛋白尿,血清尿素,和肌酐),和增加的伴侣能力(HSP70)。LysVCZn对这些参数的影响比单独的Lys更好。
    结论:这项研究的结果表明,Lys的共同给药,一个化学伴侣,在糖尿病大鼠模型中,添加两种抗氧化剂(VC和Zn)可增强其抗糖尿病作用并预防糖尿病并发症。
    OBJECTIVE: We previously showed the beneficial effect of L-Lysine (Lys), a chemical chaperone, on reducing diabetic complications in diabetic rats and type 2 diabetic patients. Herein, we evaluated the effect of Lys co-administration with Vitamin C and Zinc (Lys+VC+Zn), in diabetic rats.
    METHODS: The streptozotocin (50 mg/Kg) was injected into male adult Wistar rats to induce diabetes. Then, different groups of normal and diabetic rats were treated with Lys and Lys+VC+Zn for five months. So, there were 0.1 % Lys in the drinking water of both groups. The control groups received water alone. During the experiment, the body weight, and various parameters were determined in the blood, serum/plasma, and urine of the rats.
    RESULTS: The determination of biochemical indexes confirmed diabetes induction and its complications in rats. Treatment with either Lys or Lys+VC+Zn resulted in reduced blood glucose and protein glycation (decreasing AGEs and HbA1c), increased insulin secretion, alleviated insulin resistance and HOMA-IR, improved lipid profile and HDL functionality (LCAT and PON1), enhanced antioxidant status (FRAP and AOPP), improved kidney function (decreased microalbuminuria, serum urea, and creatinine), and increased chaperone capacity (HSP70). Lys+VC+Zn showed better effects on these parameters than Lys alone.
    CONCLUSIONS: The results of this study indicated that co-administration of Lys, a chemical chaperone, with two antioxidants (VC and Zn) potentiates its antidiabetic effects and prevent diabetic complications in rat model of diabetes.
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  • 文章类型: Journal Article
    糖尿病并发症与醛糖还原酶(AR)和晚期糖基化终产物(AGEs)有关。使用生物测定指导的柱层析分离,从三叶草中分离出10种类黄酮和1种香豆素,并在体外测试了其对人重组AR(HRAR)和大鼠晶状体AR(RLAR)的抑制作用。普宁,那利鲁丁,和柚皮苷抑制RLAR(IC500.48-2.84μM)和HRAR(IC500.68-4.88μM)。对接模拟预测了负结合能以及与RLAR和HRAR结合袋残基的相互作用。普宁(0.1和12.5μM)防止荧光AGEs和非荧光Nε-(羧甲基)赖氨酸(CML)的形成,以及果糖-葡萄糖介导的人血清白蛋白(HSA)的蛋白质糖基化和氧化。Prunin抑制了HSA的β-交叉淀粉样蛋白结构的形成。这些结果表明,prunin抑制氧化依赖性蛋白质损伤,年龄形成,AR,这可能有助于预防糖尿病并发症。
    Diabetes complications are associated with aldose reductase (AR) and advanced glycation end products (AGEs). Using bioassay-guided isolation by column chromatography, 10 flavonoids and one coumarin were isolated from Poncirus trifoliata Rafin and tested in vitro for an inhibitory effect against human recombinant AR (HRAR) and rat lens AR (RLAR). Prunin, narirutin, and naringin inhibited RLAR (IC50 0.48-2.84 μM) and HRAR (IC50 0.68-4.88 μM). Docking simulations predicted negative binding energies and interactions with the RLAR and HRAR binding pocket residues. Prunin (0.1 and 12.5 μM) prevented the formation of fluorescent AGEs and nonfluorescent Nε-(carboxymethyl) lysine (CML), as well as the fructose-glucose-mediated protein glycation and oxidation of human serum albumin (HSA). Prunin suppressed the formation of the β-cross-amyloid structure of HSA. These results indicate that prunin inhibits oxidation-dependent protein damage, AGE formation, and AR, which may help prevent diabetes complications.
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  • 文章类型: Journal Article
    肥胖会导致多个器官的代谢改变,强调器官间通信在其发病机制中的作用。细胞外囊泡(EV)是生理和病理条件下的通讯剂,尽管它们与肥胖合并症有关,在这种情况下,它们的蛋白质货物在很大程度上仍然未知。要破译电动汽车中封装的消息,我们从饮食诱导的肥胖小鼠模型中分离血浆来源的EV.肥胖血浆EV显示蛋白质多样性下降,而对照EV显示蛋白质折叠功能显着富集,强调正确折叠在维持代谢稳态中的重要性。以前,我们发现肠道衍生的电动汽车蛋白质组对肥胖具有特殊的意义。这里,我们比较了血浆和肠道电动汽车,并确定了四种蛋白质在两种电动汽车的对照状态下完全存在,通过分析血液来源的电动汽车,揭示了对肠道健康进行非侵入性评估的潜力。鉴于翻译后修饰(PTM)的相关性,我们观察到在肥胖的肠道电动汽车中染色质相关蛋白从糖化到乙酰化的转变,提示肥胖期间靶向DNA转录的调节机制。这项研究为电动汽车和蛋白质PTM在肥胖背后的复杂机制中的新作用提供了有价值的见解。为未来的研究提供潜在的生物标志物和途径。
    Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are communication agents in physiological and pathological conditions, and although they have been associated with obesity comorbidities, their protein cargo in this context remains largely unknown. To decipher the messages encapsulated in EVs, we isolated plasma-derived EVs from a diet-induced obese murine model. Obese plasma EVs exhibited a decline in protein diversity while control EVs revealed significant enrichment in protein-folding functions, highlighting the importance of proper folding in maintaining metabolic homeostasis. Previously, we revealed that gut-derived EVs\' proteome holds particular significance in obesity. Here, we compared plasma and gut EVs and identified four proteins exclusively present in the control state of both EVs, revealing the potential for a non-invasive assessment of gut health by analyzing blood-derived EVs. Given the relevance of post-translational modifications (PTMs), we observed a shift in chromatin-related proteins from glycation to acetylation in obese gut EVs, suggesting a regulatory mechanism targeting DNA transcription during obesity. This study provides valuable insights into novel roles of EVs and protein PTMs in the intricate mechanisms underlying obesity, shedding light on potential biomarkers and pathways for future research.
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