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氧化应激


诱导抗氧化有关的酶类产生:
•超氧化物歧化酶(SOD)、 •过氧化氢酶(CAT)、 •谷胱甘肽过氧化物酶(GSH-Px) 等。
减轻氧化硝基化损伤
维持金属离子稳态
降低心脏自噬作用
金属离子 稳态
转运 代谢
重金属 清道夫
•缓解金属 离子浓度 过高造成 的结构损 伤 •解除金属 诱导的细 胞毒性 •保护心肌 细胞
非特异性
不产生新氧化物质
靶向分布
安全性
• MT抗氧化过程中不影响心肌细胞正常功能表达
减轻氧化硝基化损伤
维持金属离子稳态
降低心脏自噬作用
氧化还原循环:
•低氧化水平时,当环境氧化程度 因为某些因素例如谷光甘肽 (GSH)/氧化型谷胱甘肽(GSSG) 比例增加而减弱,Zn结合MT-硫醇 生成MT; •高氧化水平时,随着在ROS或 GSSG存在下环境氧化程度增加, MT在Se催化作用下转为MT-硫醇 结合自由基,Zn被释放出来作用 于蛋白质、脂质等生物大分子。
MT-mRNA
检测 金属饱和度测定法 电化学方法
质谱偶联法
巯基显色法 分 离 电泳法 色谱分析法 层析法 DEAE-Sepharose Fast Flow
凝胶电泳、毛细管电泳 高效液相色谱法(HPLC)、高效液相原子吸收法(HPLC-AAS) 离子交换层析法等
纯化
抗酸 抗碱
高金属 含量
低分子 量
高诱导 性
减轻氧化硝基化损伤
维持金属离子稳态
降低心脏自噬作用
PI3K(I) -Akt信 号通路
代谢失 调
自噬信 号级联
减少心 脏畸形
氧化应激
• 指机体在内外环境有害刺激的条件下,体内产生活性氧自由基(ROS)和 活性氮自由基(RNS)所引起的细胞和组织的生理和病理反应。 • 可以直接或间接氧化或损伤DNA、蛋白质和脂质,可诱发基因突变、蛋白 质变性和脂质过氧化,被认为是人体衰老和各种重要疾病的主要危险因子。
心血管疾病
三者之间相互 作用
加重损害
血管内皮细胞 受损、血管平 滑肌受损
影响骨骼肌葡 萄糖转运作用
ACE增加与 NFκB激活炎 性过程相关基 因转录
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