C2CD4B通过PI3K/Akt/PKCα信号通路引起氧化应激和血管功能障碍
Paola Di Pietro1, Angela Carmelita Abate1, Valeria Prete1
1Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.
Antioxidants (Basel, Switzerland)
|January 22, 2024
概括
含有4B的C2依赖域 (C2CD4B) 通过增加氧化应激和减少氧化 (NO) 直接导致糖尿病内皮功能障碍. 抑制C2CD4B可以防止高血糖引起的血管损伤.
科学领域:
- 血管生物学 血管生物学
- 内分泌学 在内分泌学.
- 分子医学是分子医学.
背景情况:
- 糖尿病血管病症的特征是内皮功能障碍.
- 全基因组研究将2型糖尿病 (T2DM) 与含有4B (C2CD4B) 表达的C2依赖域增加联系起来.
- 在血管功能中C2CD4B的直接作用仍然未被探索.
研究的目的:
- 研究C2CD4B对血管内皮的直接影响.
- 阐明糖尿病中C2CD4B介导的内皮功能障碍背后的分子机制.
- 确定C2CD4B作为糖尿病血管病的潜在治疗点.
主要方法:
- 在高葡萄糖条件下,评估C2CD4B表达在小鼠中带动脉中.
- 利用基因淘汰来抑制C2CD4B的表达.
- 通过使用压力神经图进行了血管反应性研究.
- 测量了氧化 (NO) 的生物可用性和氧化应激 (ROS),使用二二酸盐和二乙.
- 研究了C2CD4B对人类静脉内皮细胞 (HUVECs) 内皮氧化合成酶 (eNOS) 酸化和二元化的影响.
- 检查了氨基酸3-激酶 (PI3K) /Akt/PKCα信号通路的作用.
主要成果:
- 在小鼠中腔动脉中,高葡萄糖上调C2CD4BmRNA和蛋白质.
- 基因淘汰C2CD4B可以防止高血糖引起的氧化应激,内皮功能障碍和NO损失.
- 重组C2CD4B诱导了内皮功能障碍,增加了ROS,并减少了NO的产生.
- 在HUVEC中,C2CD4B增加了抑制性eNOS酸化 (Thr495) 并降低了eNOS二分化.
- PI3K/Akt/PKCα通路抑制剂减弱了C2CD4B诱导的血管损伤.
结论:
- C2CD4B直接影响血管内皮的功能.
- C2CD4B通过PI3K/Akt/PKCα信号通路调解内皮质功能障碍.
- C2CD4B是一种新的治疗点,用于预防糖尿病引起的内皮功能障碍中氧化应激.
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