Activation of transcription factor nrf2 by isothiocyanates and prevention of cellular senescence in vitro

异硫氰酸盐激活转录因子 nrf2 并预防体外细胞衰老

• 批准号: BB/D006295/2
• 负责人: Paul Thornalley
• 金额: $ 25.93万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD006295%2F2
• 关键词: Activation; transcription; factor; nrf2; isothiocyanates

Growing old takes a continuing toll on our skin, tissues and general health. An understanding of the ageing process and appropriate drugs or nutritional supplements to slow the process down may help us be healthier in old age. Spontaneous damage to proteins and DNA accumulates in cells during their life and contributes to the ageing effects. This can probably be resisted by increasing the activity of enzymes that protect proteins and DNA from damage. One such enzyme is glyoxalase I (GLO1). GLO1 protects proteins and DNA directly against damage from reactive sugar-derived molecules and protects indirectly against oxidative damage and impairment of cell respiration. Increasing the amount of GLO1, by overexpression of the gene for GLO1 in experimental conditions, has recently been shown to produce a 40% increase in lifespan of a small worm (nematode) commonly used as an experimental model of ageing. I have recently found that GLO1 can also be increased by compounds absorbed from Brassica vegetables such as cabbage, broccoli and others. These compounds, isothiocyanates, activate processes that affect the regulation of the GLO1 gene. I think it highly likely that isothiocyanates may slow the ageing process by increasing GLO1 expression / with probably also other effects. To test this, in this project I will use a human cell culture model of ageing. I will test if overexpression of GLO1 achieved by genetic techniques prevents ageing of human cells / measuring the expected decrease in damage to protein and DNA. I will then see and if this can also be achieved by induction of GLO1 gene expression by isothiocyanates. A successful outcome will give the first suggestions that eating your greens may slow the ageing process.

变老会对我们的皮肤、组织和整体健康造成持续的损害。了解衰老过程以及减缓衰老过程的适当药物或营养补充剂可能有助于我们在老年时更加健康。对蛋白质和 DNA 的自发损伤会在细胞的生命周期中不断积累，并导致衰老效应。这或许可以通过增加保护蛋白质和 DNA 免受损害的酶的活性来抵抗。其中一种酶是乙二醛酶 I (GLO1)。 GLO1 直接保护蛋白质和 DNA 免受活性糖衍生分子的损伤，并间接保护免受氧化损伤和细胞呼吸损伤。最近研究表明，通过在实验条件下过度表达 GLO1 基因来增加 GLO1 的数量，可以使通常用作衰老实验模型的小蠕虫（线虫）的寿命延长 40%。我最近发现，从卷心菜、西兰花等甘蓝类蔬菜中吸收的化合物也可以增加 GLO1。这些化合物（异硫氰酸盐）会激活影响 GLO1 基因调节的过程。我认为异硫氰酸盐很可能通过增加 GLO1 表达来减缓衰老过程/可能还有其他作用。为了测试这一点，在这个项目中我将使用人类细胞培养衰老模型。我将测试通过基因技术实现的 GLO1 过度表达是否可以防止人类细胞衰老/测量蛋白质和 DNA 损伤的预期减少。然后我将看看这是否也可以通过异硫氰酸盐诱导 GLO1 基因表达来实现。成功的结果将给出第一个建议：吃蔬菜可以延缓衰老过程。

项目成果

Preparation of nucleotide advanced glycation endproducts--imidazopurinone adducts formed by glycation of deoxyguanosine with glyoxal and methylglyoxal.

• DOI: 10.1196/annals.1433.037
• 发表时间: 2008-04
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Fleming T;Rabbani N;Thornalley PJ
• 通讯作者: Thornalley PJ

Measurement of glyoxalase activities.

• DOI: 10.1042/bst20140010
• 发表时间: 2014-04-01
• 期刊: Biochemical Society transactions
• 影响因子: 3.9
• 作者: Arai, Makoto;Nihonmatsu-Kikuchi, Naomi;Thornalley, Paul J
• 通讯作者: Thornalley, Paul J

Aging-Dependent Reduction in Glyoxalase 1 Delays Wound Healing

• DOI: 10.1159/000351628
• 发表时间: 2013-01-01
• 期刊: GERONTOLOGY
• 影响因子: 3.5
• 作者: Fleming, Thomas H.;Theilen, Till-Martin;Nawroth, Peter P.
• 通讯作者: Nawroth, Peter P.