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高脂饮食会改变小鼠结肠黏蛋白的寡糖链。

High-fat diet alters the oligosaccharide chains of colon mucins in mice.

作者信息

Mastrodonato Maria, Mentino Donatella, Portincasa Piero, Calamita Giuseppe, Liquori Giuseppa Esterina, Ferri Domenico

机构信息

Department of Biology, "Aldo Moro" University, Via Orabona, 4, 70125, Bari, Italy,

出版信息

Histochem Cell Biol. 2014 Oct;142(4):449-59. doi: 10.1007/s00418-014-1221-2. Epub 2014 Apr 26.

Abstract

Mucins are high molecular weight epithelial proteins, strongly glycosylated, and are the main component of the mucus. Since mucus secretion can be altered in diseases, colon mucins can be regarded as a biomarker of chronic inflammatory bowel diseases or preneoplastic changes. Conventional histochemistry and lectin histochemistry combined with chemical treatment and enzymatic digestion were carried out to analyze the colon mucins in mice fed a high-fat diet for 25 weeks, a period sufficient to induce simple liver steatosis, to check whether the carbohydrate features of mucus can be altered by an inadequate diet. An increase in the sialo/sulfomucins ratio with respect to control mice, assessed by computerized image analysis, was observed in the colon, although differences in sialic acid acetylation between control and mice fed a high-fat diet were not found. High-fat diet was also associated with altered lectin-binding pattern of the mucus, with a probable shortening of oligosaccharide chains of glycoproteins. This pattern was leading to over-expression of Galβ1,3GalNAc terminal dimers (TF antigen) and GalNAc terminal residues (Tn antigen). This altered composition of mucins can be related to a defect in the process of glycosylation, or to incomplete maturation of goblet cells, and may be an early indication of preneoplastic and neoplastic changes. In conclusion, our findings confirm that a fatty-rich diet (Western-style diet) induces alteration of mucins and may be associated with colon diseases. Our investigation corroborates the usefulness of lectins histochemistry in the early diagnosis of prepathological states of the colon.

摘要

黏蛋白是高分子量的上皮蛋白,高度糖基化,是黏液的主要成分。由于疾病时黏液分泌会发生改变,结肠黏蛋白可被视为慢性炎症性肠病或肿瘤前病变的生物标志物。对喂食高脂饮食25周(足以诱发单纯性肝脂肪变性)的小鼠结肠黏蛋白进行了传统组织化学和凝集素组织化学,并结合化学处理和酶消化,以检查饮食不当是否会改变黏液的碳水化合物特征。通过计算机图像分析评估,发现与对照小鼠相比,结肠中唾液酸/硫酸黏蛋白的比例增加,尽管未发现对照小鼠与喂食高脂饮食小鼠之间唾液酸乙酰化存在差异。高脂饮食还与黏液的凝集素结合模式改变有关,可能导致糖蛋白寡糖链缩短。这种模式导致Galβ1,3GalNAc末端二聚体(TF抗原)和GalNAc末端残基(Tn抗原)过度表达。黏蛋白组成的这种改变可能与糖基化过程缺陷或杯状细胞成熟不完全有关,可能是肿瘤前和肿瘤性变化的早期迹象。总之,我们的研究结果证实,富含脂肪的饮食(西式饮食)会导致黏蛋白改变,并可能与结肠疾病有关。我们的研究证实了凝集素组织化学在结肠病理前状态早期诊断中的有用性。

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