氨酸以ESCRT-依赖的方式被纳入细胞外囊泡,并调节衰老
S Iglesias-Fortes1, A C Lockwood2, C González-Blanco2
1Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, Ciudad Universitaria, 28040 Madrid, Spain.
Biochimica et biophysica acta. Molecular basis of disease
|February 1, 2025
概括
人类氨酸 (hIAPP) 通过依赖ESCRT的途径聚集在细胞外囊泡 (EVs),影响胰腺β细胞. Resveratrol可以缓解高葡萄糖诱导的衰老,这表明2型糖尿病的治疗潜力.
科学领域:
- 内分泌学和新陈代谢学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 2型糖尿病开始于胰腺β细胞的胰岛素抵抗和补偿性高胰岛素血症.
- 贝塔细胞中的氨酸 (岛屿氨酸聚酸,IAPP) 聚合有助于它们的功能障碍和损失.
- 特定物种的氨酸聚合,就像人类的IAPP一样,与非氨酸原性动物氨酸不同,与疾病发病有关.
研究的目的:
- 为了研究人类氨酸 (hIAPP) 融入胰腺β细胞中的细胞外囊泡 (EVs).
- 探索hIAPP纳入EVs对关键细胞信号通路的影响,包括mTORC1,内质网膜应激和衰老.
- 确定中性纤维肌酶抑制剂GW4869和复星对hIAPP-EV相互作用和β细胞衰老的作用.
主要方法:
- 使用了INS1E-hIAPP细胞,胰腺β细胞系过度表达人类氨酸.
- 通过对运输 (ESCRT) 依赖机制所需的内体组分复合体,研究了将氨酸纳入EV中.
- 分析了GW4869 (EV生物发生抑制剂) 和高葡萄糖条件对氨酸-EV关联和囊泡大小的影响.
- 在各种治疗条件下评估了白醇对细胞衰老的影响.
主要成果:
- 人类氨酸以依赖于ESCRT的方式被纳入EV.
- 高葡萄糖或GW4869治疗增加了可溶性氨酸融入EVs,导致较大的囊泡大小 (微囊泡).
- ресвератрол诱导了前期衰老的表型,但在INS1E-hIAPP细胞中逆转了高葡萄糖或GW4869相关的衰老.
结论:
- 氨基酸可以通过依赖ESCRT的途径被招募到电动汽车中.
- 调节EV生物发生会影响氨酸的结合和囊泡特征.
- Resveratrol在诱导胰腺β细胞衰老方面发挥着重要作用,可能为2型糖尿病并发症提供治疗途径.
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