作为ER的陪伴者,BIP保护微细胞免受ER压力介导的高血糖症中的亡
Antonisamy William James1, Ghaith A Bahader1, Mohammad Albassan1
1Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH, USA.
Neurochemistry international
|July 16, 2023
概括
免疫球蛋白重链蛋白 (BIP) 的结合,一个ER伴侣,在高血糖期间保护微细胞免受亡. 在高葡萄糖条件下降低BIP水平会增加细胞死亡,但BIP诱导剂可以恢复功能,表明治疗潜力.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 内分泌学 在内分泌学.
背景情况:
- 免疫球蛋白重链蛋白 (BIP) 的结合是蛋白质组装中至关重要的内分泌网膜 (ER) 主要伴侣.
- 微质在中枢神经系统中起着至关重要的作用,应对损伤并清除细胞碎片.
- 在高血糖条件下BIP在微质功能中的作用尚不清楚.
研究的目的:
- 在高血糖期间研究BIP在微质功能中的分子机制.
- 探索BIP对微质中高血糖引起的亡的保护作用.
主要方法:
- 在小鼠中使用链条毒素 (STZ) 诱导高血糖,在高葡萄糖的HMC3微细胞中诱导高血糖.
- 分析了ER伴侣表达,ER压力,亡标志物 (CHOP,Bax,Bad,分裂的caspase-3) 和活性氧物种 (ROS).
- 评估了BIP诱导剂 (化合物X) 对亡和ER压力的影响.
主要成果:
- 高血糖症显著降低了HMC3细胞中的BIP蛋白表达.
- 降低BIP水平与亡,ER压力和ROS产生增加相关.
- 用BIP诱导剂X治疗恢复了BIP表达,抑制了ER压力,并减少了亡.
结论:
- 在高血糖条件下,ER陪伴者BIP对于维持微质功能和预防亡至关重要.
- BIP的失调有助于微质功能障碍和高血糖症中的亡.
- 针对BIP可能为与微质功能障碍相关的神经退行性疾病提供一种新的治疗策略.
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