TP53/p53 促进脂肪细胞因压力诱导的外体和蛋白质分泌
Yimao Huang1, Ann V Hertzel1, Shayla R Fish1
1Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN.
Diabetes
|June 22, 2023
概括
脂解刺激和细胞应激促进脂肪细胞衍生的细胞外囊泡 (AdEVs) 和脂肪酸结合蛋白4 (FABP4) 的分泌. 这个过程依赖于瘤抑制剂p53,影响脂肪平衡和代谢疾病.
科学领域:
- 细胞生物学 细胞生物学
- 代谢性疾病研究研究
- 分子内分泌学分子内分泌学
背景情况:
- 脂肪细胞在脂解刺激时分泌脂肪酸,细胞外囊泡 (AdEV) 和像FABP4这样的蛋白质.
- 这些分泌物影响脂肪组织的平衡和代谢疾病的发展.
- 调节这些分泌的精确机制,特别是在压力下,需要进一步阐明.
研究的目的:
- 研究p53在调节脂肪细胞中ADEV和FABP4分泌中的作用.
- 为了确定脂解信号和细胞压力因素是否激活p53依赖的分泌通路.
- 探索对脂肪平衡和代谢疾病的影响.
主要方法:
- 使用3T3-L1和OP9脂肪细胞细胞培养物进行体外研究.
- 采用质谱法来分析脂溶性分泌体.
- 通过使用MDM2抗体努特林和基因毒素多克索鲁比来研究p53激活.
- 在p53淘汰赛小鼠和ERCC1-/Δ-haploinsufficient小鼠中比较蛋白质和AdEV分泌.
主要成果:
- 脂解信号以脂酶依赖的脂肪甘油三酶方式激活p53.
- 药理上抑制p53降低了AdEV和FABP4的分泌.
- 激活p53增强的ADEV和非AdEV蛋白质分泌.
- 在p53-/-小鼠中,血清FABP4和ADEV蛋白减少.
- 多克索鲁比以p53依赖的方式增加了AdEV蛋白和FABP4分泌.
- 缺乏ERCC1-/Δ-哈普洛因的小鼠显示p53升高和血清FABP4.4增加.
结论:
- 脂解信号和细胞压力因素 (例如,DNA损伤) 诱导脂肪细胞分泌AdEV和FABP4.
- 这种分泌过程是由p53激活介导的.
- 这些发现强调了p53在调节脂肪细胞分泌物的新作用及其对代谢健康的潜在影响.
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