Identification of Inhibitors Against BAK Pore Formation using an Improved in vitro Assay System

Bulletin of the Korean chemical society

Kyoung Joon Oh¹  Won-Kyu Lee¹  Yeon Gyu Yu¹  Seong-Soo Song¹  Sreevidya Aluvila¹ 

关键词: BAK;    BAX;    Trifluoperazine;    Apoptosis;    High throughput;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

The pro-apoptotic BCL-2 family protein BID activates BAK and/or BAX, which form oligomeric pores in the mitochondrial outer membrane. This results in the release of cytochrome c into the cytoplasm, initiating the apoptotic cascade. Here, we utilized liposomes encapsulating sulfo-rhodamine at a controlled temperature to improve upon a previously reported assay system with enhanced sensitivity and specificity for measuring membrane permeabilization by BID-dependent BAK activation. BAK activation was inhibited by BCL-XL protein but not by a mutant protein with impaired anti-apoptotic activity. With the assay system, we screened a chemical library and identified several compounds including trifluoperazine, a mitochondrial apoptosisinduced channel blocker. It inhibited BAK activation by direct binding to BAK and blocking the oligomerization of BAK.

【 授权许可】

Unknown