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

Index: Cell. Mol. Life Sci. 67(15) , 2665-78, (2010)

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Abstract

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.