Cellular and Molecular Life Sciences 2010-08-01

Lysosomal chymotrypsin B potentiates apoptosis via cleavage of Bid.

Kai Zhao, Xingyu Zhao, Yaping Tu, Qi Miao, Dongxu Cao, Wenjuan Duan, Yang Sun, Jincheng Wang, Taotao Wei, Fuyu Yang

文献索引：Cell. Mol. Life Sci. 67(15) , 2665-78, (2010)

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摘要

We have reported that chymotrypsin B (CtrB) is not just a digestive enzyme but is also stored in lysosomes. Herein, we demonstrated a broad distribution of CtrB and explored the involvement of CtrB in apoptosis. Exposure of RH-35 cells to H(2)O(2) or palmitate induced the redistribution of lysosomal CtrB into the cytoplasm as a result of lysosomal membrane permeabilization (LMP). Suppression of CtrB significantly blocked apoptosis, while overexpression of CtrB sensitized apoptosis markedly. CtrB could cleave Bid under neutral conditions. In RH-35 cells with Bid silenced, apoptosis induced by CtrB protein was attenuated, suggesting that CtrB mediates apoptosis of RH-35 cells mainly through processing Bid. Our data also suggest that LMP occurs earlier than mitochondrial outer membrane permeabilization; Bid activation initiated by caspase-8 might be reinforced by CtrB in consequence of LMP, which causes a positive feedback loop leading to the accumulation of tBid, and results in lysosome- and mitochondrion-dependent apoptosis.