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

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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.

Original languageEnglish (US)
Pages (from-to)2665-2678
Number of pages14
JournalCellular and Molecular Life Sciences
Volume67
Issue number15
DOIs
StatePublished - Aug 1 2010

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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    Zhao, K., Zhao, X., Tu, Y., Miao, Q., Cao, D., Duan, W., Sun, Y., Wang, J., Wei, T., & Yang, F. (2010). Lysosomal chymotrypsin B potentiates apoptosis via cleavage of Bid. Cellular and Molecular Life Sciences, 67(15), 2665-2678. https://doi.org/10.1007/s00018-010-0356-0