The microbiota catabolites of quercetin glycosides concertedly enhance the resistance against acetaldehyde-induced oxidative stress
The microbiota catabolites of quercetin glycosides concertedly enhance the resistance against acetaldehyde-induced oxidative stress
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槲皮素苷的微生物分解代谢物协同增强对乙醛诱导的氧化应激的抵抗力
DOI：
10.1080/10715762.2022.2159820
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发表时间：
2022
影响因子：
3.3
通讯作者：
Nakamura Yoshimasa
中科院分区：
文献类型：
--
作者：
Li Kexin;Wu Hongyan;Kidawara Minori;Lin Yun;Satoh Ayano;Zhang Gongliang;Munemasa Shintaro;Murata Yoshiyuki;Nakamura Toshiyuki;Nakamura Yoshimasa
3，4-二羟基苯乙酸（DOPAC）和3-羟基苯乙酸（OPAC）是由肠道微生物群产生的槲皮素糖苷（如来自洋葱的槲皮素4′-O-β-葡萄糖苷）的主要催化剂。虽然每一种分解代谢产物都有保护细胞免受乙酰丙酮诱导的细胞毒性的报道，但它们的联合作用仍有待澄清。本研究的目的是确定DOPAC和OPAC的组合是否增强了对乙酰丙酮诱导的肝细胞氧化应激的抵抗力。DOPAC（5 μM）和OPAC（5 μM）的组合预处理显示出对乙醛和过氧化氢诱导的细胞毒性的显著保护，即使相同浓度的每种化合物没有。这种组合还显著抑制细胞内二氯荧光素二乙酸酯可检测的活性氧（ROS）水平，而单独处理则略有抑制，这表明ROS或增强ROS产生的化合物的减少机制参与了细胞保护作用。联合处理不仅显著增强了乙醛脱氢酶（ALDHs）的基因表达，而且还增强了谷胱甘肽（GSH）合成的第一限速酶谷氨酸-半胱氨酸连接酶（Glutamate-Cysteine Ligase）的催化亚基的基因表达。因此，DOPAC和OPAC都能提高细胞内GSH水平和总ALDH活性。通过使用GSH生物合成抑制剂丁噻托溴铵亚砜亚胺的实验证实了GSH参与细胞保护以及组合的ALDH上调。综上所述，本研究结果表明，槲皮素微生物群通过GSH依赖性ALDH上调预增强抗氧化应激能力，协同保护细胞免受乙醛侵害。
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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影响因子：
4.4
作者：
Jamal, Mostofa;Ameno, Kiyoshi;Kinoshita, Hiroshi
通讯作者：
Kinoshita, Hiroshi
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影响因子：
3.6
作者：
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通讯作者：
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影响因子：
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作者：
P. Pappas;V. Vasiliou;M. Karageorgou;P. Stefanou;M. Marselos
通讯作者：
M. Marselos
影响因子：
3.2
作者：
Hsu-Sheng Yu;T. Oyama;T. Isse;Kyoko Kitakawa;M. Ogawa;T. Pham;T. Kawamoto
通讯作者：
Hsu-Sheng Yu;T. Oyama;T. Isse;Kyoko Kitakawa;M. Ogawa;T. Pham;T. Kawamoto
影响因子：
6.1
作者：
Mullen, William;Rouanet, Jean-Max;Crozier, Alan
通讯作者：
Crozier, Alan