Furuhashi Mai, Hatasa Yukinori, Kawamura Sae, Shibata Takahiro, Akagawa Mitsugu, Uchida Koji
Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya 464-8601, Japan.
PRESTO, Japan Science and Technology Agency , Kawaguchi, Saitama 332-0012, Japan.
Biochemistry. 2017 Sep 5;56(35):4701-4712. doi: 10.1021/acs.biochem.7b00409. Epub 2017 Aug 23.
Polyphenols have received a significant amount of attention in disease prevention because of their unique chemical and biological properties. However, the underlying molecular mechanism for their beneficial effects remains unclear. We have now identified a polyphenol as a source of innate epitopes detected in natural IgM and established a unique gain-of-function mechanism in the formation of innate epitopes by polyphenol via the polymerization of proteins. Upon incubation with bovine serum albumin (BSA) under physiological conditions, several polyphenols converted the protein into the innate epitopes recognized by the IgM Abs. Interestingly, piceatannol, a naturally occurring hydroxylated analogue of a red wine polyphenol, resveratrol, mediated the modification of BSA, whose polymerized form was specifically recognized by the IgMs. The piceatannol-mediated polymerization of the protein was associated with the formation of a lysine-derived cross-link, dehydrolysinonorleucine. In addition, an oxidatively deaminated product, α-aminoadipic semialdehyde, was detected as a potential precursor for the cross-link in the piceatannol-treated BSA, suggesting that the polymerization of the protein might be mediated by the oxidation of a lysine residue by piceatannol followed by a Schiff base reaction with the ε-amino group of an unoxidized lysine residue. The results of this study established a novel mechanism for the formation of innate epitopes by small dietary molecules and support the notion that many of the beneficial effects of polyphenols could be attributed, at least in part, to their lysyl oxidase-like activity. They also suggest that resveratrol may have beneficial effects on human health because of its conversion to piceatannol.
由于其独特的化学和生物学特性，多酚在疾病预防方面受到了广泛关注。然而，其有益作用的潜在分子机制仍不清楚。我们现已确定一种多酚是天然IgM中检测到的天然表位的来源，并通过蛋白质聚合建立了多酚形成天然表位的独特功能获得机制。在生理条件下与牛血清白蛋白（BSA）孵育后，几种多酚将该蛋白质转化为被IgM抗体识别的天然表位。有趣的是，白藜芦醇，一种天然存在的红酒多酚白藜芦醇的羟基化类似物，介导了BSA的修饰，其聚合形式被IgM特异性识别。白藜芦醇介导的蛋白质聚合与赖氨酸衍生的交联物脱氢赖氨酸的形成有关。此外，在白藜芦醇处理的BSA中检测到一种氧化脱氨基产物α-氨基己二酸半醛作为交联的潜在前体，这表明蛋白质的聚合可能是由白藜芦醇对赖氨酸残基的氧化，然后与未氧化的赖氨酸残基的ε-氨基发生席夫碱反应介导的。这项研究的结果建立了一种由膳食小分子形成天然表位的新机制，并支持了多酚的许多有益作用至少部分可归因于其赖氨酰氧化酶样活性的观点。它们还表明，白藜芦醇可能因其转化为白藜芦醇而对人类健康有益。
