KLHL3依赖的WNK4降解受通过和自途径的影响
Siqi Ying1, Qin Guo2, Chong Zhang3
1Department of Nephrology, Jing'an District Center Hospital of Shanghai, Fudan University, Shanghai, 200040, China.
BMC nephrology
|July 22, 2023
概括
饮食中的含量会通过脱和自途径影响WNK4蛋白质的降解. 低会增加WNK4的丰富性和活性,可能会影响高血压和功能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 脏生理学 脏生理学
背景情况:
- 凯尔奇类蛋白3 (KLHL3) - 库林3 (CUL3) E3结合酶针对无-氨酸激酶4 (WNK4) 进行无处不在.
- 损坏的WNK4无处可见性与家族高血压 (FHHt) 和过度活跃的 thiazide-sensitive 化共载体 (NCC) 有关.
- 饮食中缺乏会激活脏远端卷状管 (DCT) 中的NCC,但涉及WNK4的潜在机制尚不清楚.
研究的目的:
- 研究在调节WNK4降解中的作用.
- 阐明在介导的WNK4调节中和自途径的参与.
- 了解连接,WNK4和NCC活动的分子机制.
主要方法:
- 在体外研究中,使用感染了WNK4和KLHL3的HEK293细胞,并使用不同度的和缩抑制剂 (MLN4924) 和自抑制剂进行治疗.
- 在体内研究中,小鼠接受低或高饮食,并接受MLN4924治疗.
- 西方涂抹检测WNK4,化WNK4 (pWNK4),KLHL3,NEDD8,LC3和P62的表达.
主要成果:
- 抑制化增加了WNK4的丰度和化,在体外和体内.
- 低的饮食导致pWNK4,WNK4,NEDD8和KLHL3.3的丰度增加.
- 自抑制部分减轻了对WNK4丰度和活性的影响.
结论:
- 通过无和自途径复杂地调节WNK4的降解.
- 低的条件似乎可以通过这些途径激活WNK4.
- 需要进一步的研究才能充分阐明具体的机制.
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