槲皮素苷的微生物群分解产物协同增强对乙醛诱导的氧化应激的抵抗力。

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kexin Li, Hongyan Wu, Minori Kidawara, Yun Lin, Ayano Satoh, Gongliang Zhang, Shintaro Munemasa, Yoshiyuki Murata, Toshiyuki Nakamura, Yoshimasa Nakamura
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引用次数: 1

摘要

3,4-二羟基苯基乙酸(DOPAC)和3-羟基苯基乙酸(OPAC)是槲皮素苷的主要分解代谢物,如洋葱中的槲皮素4′-O-β-葡萄糖苷,由肠道微生物群产生。虽然每一种分解代谢物都有保护细胞免受乙醛诱导的细胞毒性的报道,但它们结合的效果仍有待阐明。本研究的目的是确定DOPAC和OPAC联合使用是否能增强培养的肝细胞对乙醛诱导的氧化应激的抵抗力。DOPAC (5 μM)和OPAC (5 μM)联合预处理对乙醛和过氧化氢诱导的细胞毒性具有显著的保护作用,而相同浓度的化合物对乙醛和过氧化氢诱导的细胞毒性没有显著的保护作用。该组合还显著抑制了细胞内二乙酸二氯荧光素-可检测的活性氧(ROS)水平,而单独处理则略有抑制,这表明ROS的减少机制或增强ROS产生的化合物参与了细胞保护作用。组合处理不仅显著提高了醛脱氢酶(ALDHs)的基因表达,而且显著提高了谷胱甘肽合成第一限速酶——催化亚基谷氨酸-半胱氨酸连接酶的基因表达。因此,DOPAC + OPAC可提高细胞内GSH水平和ALDH总活性。使用GSH生物合成抑制剂丁硫氨酸亚砜进行的实验证实了GSH参与细胞保护和ALDH上调。综上所述,目前的结果表明,槲皮素微生物群分解代谢物通过gsh依赖性的aldh上调来预先增强抗氧化应激能力,从而共同保护细胞免受乙醛的侵害。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The microbiota catabolites of quercetin glycosides concertedly enhance the resistance against acetaldehyde-induced oxidative stress.

3,4-Dihydroxyphenylacetic acid (DOPAC) and 3-hydroxyphenylacetic acid (OPAC) are the predominant catabolites of quercetin glycosides, such as quercetin 4'-O-β-glucoside from the onion, produced by intestinal microbiota. Although each catabolite has been reported to protect the cells from acetaldehyde-induced cytotoxicity, the effect of their combination remains to be clarified. The purpose of this study was to determine whether the combination of DOPAC and OPAC enhances the resistance against the acetaldehyde-induced oxidative stress in the cultured hepatocytes. The pretreatment of the combination of DOPAC (5 μM) and OPAC (5 μM) showed significant protection against the acetaldehyde- and hydrogen peroxide-induced cytotoxicity, even though each compound at the same concentration did not. This combination also significantly inhibited the intracellular dichlorofluorescin diacetate-detectable reactive oxygen species (ROS) level, whereas the solo treatment did slightly, suggesting that reducing mechanisms of ROS or compounds that enhance ROS production are involved in the cytoprotective effect. The combinatory treatment significantly enhanced the gene expression of not only the aldehyde dehydrogenases (ALDHs), but also glutamate-cysteine ligase, catalytic subunit, the first rate-limiting enzyme of glutathione (GSH) synthesis. Accordingly, both the intracellular GSH level and the total ALDH activity were enhanced by DOPAC plus OPAC. Involvement of GSH in the cytoprotection as well as ALDH up-regulation by the combination was confirmed by the experiments using a GSH biosynthesis inhibitor, buthionine sulfoximine. Taken together, the present results suggested that the quercetin microbiota catabolites concertedly protect the cells from acetaldehyde through a pre-enhanced resistance against oxidative stress by the GSH-dependent up-regulation of ALDHs.

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来源期刊
Free Radical Research
Free Radical Research 生物-生化与分子生物学
CiteScore
6.70
自引率
0.00%
发文量
47
审稿时长
3 months
期刊介绍: Free Radical Research publishes high-quality research papers, hypotheses and reviews in free radicals and other reactive species in biological, clinical, environmental and other systems; redox signalling; antioxidants, including diet-derived antioxidants and other relevant aspects of human nutrition; and oxidative damage, mechanisms and measurement.
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