Lysosomal chymotrypsin B potentiates apoptosis via cleavage of Bid |
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Authors: | Kai Zhao Xingyu Zhao Yaping Tu Qi Miao Dongxu Cao Wenjuan Duan Yang Sun Jincheng Wang Taotao Wei Fuyu Yang |
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Affiliation: | (1) National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101, China;(2) Graduate University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing, 100049, China;(3) Department of Pharmacology, Creighton University School of Medicine, Omaha, NE 68178, USA |
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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 H2O2 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. |
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