轻度氧化的LDL诱导了血小板衍生的生长因子β受体通路的激活
I Escargueil-Blanc1, R Salvayre, N Vacaresse
1INSERM U-466 and the Biochemistry Department, IFR-31, CHU Rangueil, Toulouse, France.
Circulation
|October 10, 2001
概括
轻度氧化LDL (moxLDL) 通过两种不同的机制激活了血小板衍生生长因子受体β (PDGFRbeta),其中包括4-hydroxynonenal和ceramide. 这种新的途径可能有助于动脉动脉生成.
科学领域:
- 血管生物学 血管生物学
- 动脉样硬化研究 动脉样硬化研究
- 细胞信号传递 细胞信号传递
背景情况:
- 轻度氧化低密度脂蛋白 (moxLDL) 参与了动脉生成.
- moxLDL诱导蛋白质修饰和细胞内信号级联.
- 研究了moxLDL在激活血小板衍生生长因子受体β (PDGFRbeta) 的作用.
研究的目的:
- 为了确定moxLDL诱导的蛋白质修饰是否影响PDGFRbeta活性.
- 为了阐明PDGFRbeta被moxLDL激活的机制.
主要方法:
- 实验是在培养的子动脉光滑肌细胞上进行的.
- 评估了PDGFRβ 氨酸酸化和含SH2的蛋白质共免疫沉.
- 在现场和体外实验中对免疫净化PDGFRbeta进行了实验.
主要成果:
- 莫克斯LDL激活PDGFRbeta信号通路,由氨酸酸化证明.
- 通过moxLDL确定了PDGFRbeta激活的两个阶段.
- 第1阶段涉及4-hydroxynonenal诱导的PDGFRbeta adduct形成 (抗氧化剂不敏感).
- 第二阶段涉及陶胺介导的过氧化生成 (由陶胺抑制剂和抗氧化剂抑制).
- 在动脉样硬化的大动脉中检测到4-hydroxynonenal-PDGFRbeta adducts.
结论:
- 在血管壁中,moxLDL 作为自分泌媒介体起作用.
- PDGFRbeta作为氧化脂质和氧化应激的传感器.
- 建议在动脉样硬化区域激活PDGFRbeta的一个新机制.
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