Protective effects of foods rich in carotenoids against DNA damages due to reactions of chemically induced triplet states of melanin derivatives

富含类胡萝卜素的食物对化学诱导黑色素衍生物三重态反应引起的 DNA 损伤的保护作用

• 批准号: 349764062
• 负责人: Professor Dr. Volker Böhm
• 金额: --
• 依托单位: Institut für Biochemie und Molekularbiologie I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/349764062?language=en
• 关键词: Protective; effects; foods; rich; carotenoids

Carotenoids comprise a group of secondary plant constituents in our diet with photoprotective properties. Human intervention studies have proven the light-protective effects of the major carotenoids beta-carotene, lycopene and lutein. After ingestion, the compounds are absorbed and distributed via the blood stream to the target tissues (skin and eye) where they reveal preventive effects. These effects are mechanistically linked to their antioxidant properties such as quenching of light-induced excited triplet state molecules or singlet oxygen and scavenging of reactive oxygen species including superoxide or lipid peroxides, thus contributing to the prevention of photooxidative DNA damage. Upon UV-irradiation, DNA is oxidized and cyclobutane pyrimidine dimers (CPDs) are generated in light-dependent reactions. On a time scale, these processes occur directly after light-exposure. Recently, it has been shown that in addition to these direct effects, a so called dark reaction is initiated in which a time delayed (hours) formation of CPDs (dark CPDs) occurs. In a UV-induced reaction sequence, degradation products of melanin and reactive oxygen species form dioxetanes, which decompose to yield excited triplet carbonyls. Upon quenching of the excited triplet state, dark CPDs are formed. The pattern of the CPDs depends on their way of formation, and its analyses by means of HPLC-MS/MS allows to distinguish between directly and delayed formed species. Carotenoids are efficient quenchers of excited triplet carbonyls and thus should inhibit the generation of dark CPDs. In model systems and cell culture (melanocytes, skin model) carotenoids from dietary sources (carrots, tomatoes, squash) will be used to investigate their effects on the formation of dark CPDs. Key aspect is a nutritional approach to address the properties of complex food systems inhibiting biologically defined damages following UV exposure and attributing photoprotective effects to the key components and a major mechanism, namely quenching of excited triplet states.

类胡萝卜素包括一组在我们的饮食中具有光保护特性的次生植物成分。人类干预研究已经证明了主要的类胡萝卜素β-胡萝卜素，番茄红素和叶黄素的光保护作用。摄入后，这些化合物被吸收并通过血流分布到靶组织（皮肤和眼睛），在那里它们显示出预防作用。这些作用在机制上与其抗氧化特性有关，例如光诱导的激发三重态分子或单线态氧的淬灭以及活性氧物质（包括超氧化物或脂质过氧化物）的清除，从而有助于防止光氧化DNA损伤。在紫外线照射下，DNA被氧化，并在光依赖性反应中产生环丁烷嘧啶二聚体（CPD）。在时间尺度上，这些过程直接发生在曝光后。最近，已经表明，除了这些直接效应之外，还引发了所谓的暗反应，其中发生CPD（暗CPD）的延迟时间（小时）形成。在紫外线诱导的反应序列中，黑色素和活性氧的降解产物形成二氧杂环丁烷，其分解产生激发的三重态羰基。在激发三重态猝灭时，形成暗CPD。CPD的模式取决于它们的形成方式，通过HPLC-MS/MS对其进行分析可以区分直接形成的物质和延迟形成的物质。类胡萝卜素是激发三重态羰基的有效淬灭剂，因此应抑制暗CPD的产生。在模型系统和细胞培养（黑色素细胞，皮肤模型）类胡萝卜素从饮食来源（胡萝卜，西红柿，南瓜）将被用来研究其对形成黑暗的CPD的影响。关键方面是解决复杂食物系统的特性的营养方法，其抑制紫外线暴露后的生物学定义的损害，并将光保护作用归因于关键组分和主要机制，即激发三重态的淬灭。

项目成果

Carbon monoxide releasing molecule 401 (CORM-401) modulates phase I metabolism of xenobiotics.

• DOI: 10.1016/j.tiv.2019.04.018
• 发表时间: 2019-09
• 期刊: Toxicology in vitro : an international journal published in association with BIBRA
• 作者: Moritz Walter;W. Stahl;P. Brenneisen;A. Reichert;David Stucki

Carbon monoxide exposure activates ULK1 via AMPK phosphorylation in murine embryonic fibroblasts.

一氧化碳暴露通过小鼠胚胎成纤维细胞中的 AMPK 磷酸化激活 ULK1

• DOI: 10.1024/0300-9831/a000714
• 发表时间: 2021
• 期刊: International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition
• 作者: Stucki D;Westhoff P;Brilhaus D;Weber APM;Brenneisen P;Stahl W
• 通讯作者: Stahl W

Bioavailability of Naringenin Chalcone in Humans after Ingestion of Cherry Tomatoes.

• DOI: 10.1024/0300-9831/a000574
• 发表时间: 2020-10
• 期刊: International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition
• 作者: Carina Kolot;A. Rodriguez-Mateos;R. Feliciano;K. Bottermann;W. Stahl

Effects of frequently applied carbon monoxide releasing molecules (CORMs) in typical CO-sensitive model systems - A comparative in vitro study.

• DOI: 10.1016/j.abb.2020.108383
• 发表时间: 2020-04
• 期刊: Archives of biochemistry and biophysics
• 影响因子: 3.9
• 作者: David Stucki;Heide Krahl;Moritz Walter;Julia Steinhausen;K. Hommel;P. Brenneisen;W. Stahl

Endogenous Carbon Monoxide Signaling Modulates Mitochondrial Function and Intracellular Glucose Utilization: Impact of the Heme Oxygenase Substrate Hemin

内源性一氧化碳信号调节线粒体功能和细胞内葡萄糖利用：血红素加氧酶底物血红素的影响

• DOI: 10.3390/antiox9080652
• 发表时间: 2020
• 期刊: Antioxidants
• 影响因子: 7
• 作者: Stucki D;Steinhausen J;Westhoff P;Krahl H;Brilhaus D;Massenberg A;Weber APM;Reichert AS;Brenneisen P;Stahl W
• 通讯作者: Stahl W