Keap1翻译后修饰调控氧化应激相关疾病
Post-translational modification of Keap1 regulates oxidative stress-related diseases
瞿瑛 1毛彩云 2钟晴 2张蓉 2宋运佳2
作者信息
- 1. 黑龙江中医药大学,黑龙江 哈尔滨 150040
- 2. 黑龙江中医药大学 基础医学院 药理教研组,黑龙江 哈尔滨 150040
- 折叠
摘要
Keap1-Nrf2 信号通路的激活是细胞对抗氧化应激的重要机制.氧化应激条件下,Keap1 受到谷胱甘肽化、烷基化以及S-巯基化等翻译后修饰(PTM)的影响,与Nrf2 的结合被减弱,导致Nrf2 积累、核易位以及下游解毒和抗氧化防御蛋白质的表达和转录.Keap1 的PTM参与调控癌、帕金森病和动脉粥样硬化等多种氧化应激相关疾病,例如烷基化抑制腹主动脉瘤形成、甲基化促进乳腺癌固有抵抗以及S-巯基化改善动脉粥样硬化,为寻找新的药物靶点和生物标志物提供理论基础.
Abstract
The activation of Keap1-Nrf2 signaling pathway is an important mechanism for cells to resist oxidative stress.Under oxidative stress,Keap1 is affected by post-translational modification(PTM)such as glutathione,alky-lation and S-sulfhydrylation,which weakens its binding to Nrf2,leading to Nrf2 accumulation,nuclear translocation and the expression and transcription of downstream detoxification and antioxidant defense proteins.The PTM of Keap1 is involved in the regulation of a variety of oxidative stress-related diseases such as cancer,Parkin-son's disease and atherosclerosis.For example,alkylation inhibits abdominal aortic aneurysm formation,methylation promotes innate resistance of breast cancer,and S-sulfhydrylation improves atherosclerosis,which pro-vides a theoretical basis for finding new drug targets and biomarkers.
关键词
Keap1/氧化应激/翻译后修饰/作用机制Key words
Keap1/oxidative stress/post-translational modifications/mechanism of action引用本文复制引用
出版年
2025
国家科技期刊平台
NSTL
万方数据