Overexpression of ESCRT System Members Enhances Cells’ Ability to Cope with U18666A-Induced Cholesterol Accumulation
Jia Zhijuan, Tan Wei, Wang Yaru, Cai Ying, Chen Cheng*
U18666A is a cell-permeable amphiphilic aminosteroid that inhibits the transport of cholesterol and the formation of multivesicular bodies, promotes the accumulation of intracellular cholesterol, and causes apoptosis. We found that endosomal sorting complexes required for transport (ESCRT) system-related protein expression decreased in MLE12 cells treated by U18666A. Transgenic cell lines that overexpressed ESCRT-III system members Vps24 or Chmp1b were constructed. Compared with cells which transfected empty vector, Vps24 or Chmp1b over expression transgenic cells have an increased ability to counteract the accumulation of cholesterol and subsequent physiological effects induced by U18666A. These results suggest that U18666A may interfere with some functions of ESCRT system and provide a new approach to the prevention and treatment of cholesterol accumulation related diseases.
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