Prevention of cutaneous photoageing by dietary antioxid*

通过膳食抗氧化剂预防皮肤光老化*

• 批准号: 6524833
• 负责人: SANTOSH K KATIYAR
• 金额: $ 7.18万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6524833
• 关键词: aging; alternative medicine; antioxidants; catalase; colorimetry; diet therapy; dietary supplements; disease /disorder prevention /control; flavonoids; free radical oxygen; glutathione peroxidase; hairless mouse; hydrogen peroxide; immunocytochemistry; light adverse effect; metalloendopeptidases; mitogen activated protein kinase; nutrition related tag; oxidative stress; peroxidation; phosphorylation; plant extracts; radiation protection; skin disorder; tea; ultraviolet radiation; western blottings

DESCRIPTION (provided by applicant) Cutaneous ageing is a complex biological phenomenon consisting of 2 distinct components: (1) the intrinsic, genetically-determined degenerative ageing processes, and (2) extrinsic ageing due to exposure to the environment, paticularly solar ultraviolet (UV) light, also known as photoageing. Exposure of UV radiation, particularly UVB (290-320 nanometers), to mammalian skin is responsible for several skin disorders including photoageing, thus making it the most hazardous environmental pollutant. It is well documented that UV radiation is a potent producer of reactive oxygen species (ROS), which have 2 potentially important effects: damage of various cell components and triggering the activation of specific signaling pathways. Both of these effects can influence numerous cellular processes linked to age-related skin diseases including photoageing. One practical approach to reduce the risk of UV-induced ROS-mediated skin photoageing may be the use of dietary botanical supplements having antioxidant properties. In earlier studies, the investigators have shown that green tea polyphenols (hereafter referred as GTP) have remarkable preventive effects against UV-induced oxidative stress in the skin. The central hypothesis to be tested in this proposal is that in vivo UVB exposure to skin depletes antioxidant defense system and induces oxidative stress, which causes activation of extracellular signal-regulated kinase, c-Jun amino-terminal kinase and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Activation of MAPK results in phosphorylation of the transcription factors, which in turn results in upregulation of metalloproteinases (MMP) and leads to photoageing of the skin. The corollary to the hypothesis is that dietary antioxidant supplements such as GTP in drinking water to SKH-1 hairless mice will prevent UVB radiation-induced depletion of antioxidant defense system and oxidative stress, and thus oxidative stress-mediated phosphorylation of MAPK signaling pathways. The inhibition of UVB-induced oxidative stress-mediated phosphorylation of cellular signaling in vivo by GTP will result in reduction of skin photoageing incidence. Validation of this hypothesis would have major implications for the importance of oxidative stress-mediated skin ageing, as well as offering promise for the development of novel intervention approaches and strategies to prevent skin photoageing by the use of dietary antioxidant supplements.

描述（由申请人提供） 皮肤老化是一种复杂的生物现象，由两种不同的因素组成 组成部分：（1）内在的、遗传决定的退行性衰老 过程，以及（2）由于暴露于环境而导致的外在老化， 特别是太阳紫外线（UV），也称为光老化。 接触 紫外线辐射，特别是 UVB（290-320 纳米）对哺乳动物皮肤的影响 导致多种皮肤疾病，包括光老化，从而使其 最危险的环境污染物。 有充分记录表明，紫外线 辐射是活性氧 (ROS) 的有效产生者，其具有 2 潜在的重要影响：各种细胞成分的损伤和 触发特定信号通路的激活。 这两个 效应可以影响与年龄相关的皮肤相关的许多细胞过程 疾病，包括光老化。 一种降低风险的实用方法 紫外线诱导的 ROS 介导的皮肤光老化可能是使用膳食植物 具有抗氧化特性的补充剂。 在早期的研究中， 研究人员证明，绿茶多酚（以下简称绿茶多酚） GTP）对紫外线诱导的氧化应激具有显着的预防作用 皮肤。 本提案要检验的中心假设是 体内 UVB 暴露于皮肤会耗尽抗氧化防御系统并诱导 氧化应激，导致细胞外信号调节的激活 激酶、c-Jun 氨基末端激酶和 p38 丝裂原激活蛋白激酶 (MAPK) 信号通路。 MAPK 的激活导致 转录因子，进而导致上调 金属蛋白酶（MMP）并导致皮肤光老化。 推论 假设是膳食抗氧化剂补充剂（例如 GTP） 给SKH-1无毛小鼠喝水可以预防UVB辐射引起的 抗氧化防御系统和氧化应激的耗竭，因此 氧化应激介导的 MAPK 信号通路磷酸化。 这 抑制 UVB 诱导的氧化应激介导的磷酸化 GTP 体内细胞信号传导将导致皮肤光老化减少 发生率。 这一假设的验证将对以下方面产生重大影响： 氧化应激介导的皮肤老化的重要性，以及提供 开发新的干预方法和策略的承诺 通过使用膳食抗氧化剂补充剂来预防皮肤光老化。