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

Research output: Contribution to journalArticle

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

Fingerprint

Apoptosis
Lysosomes
Membranes
chymotrypsin B
Caspase 8
Palmitates
Mitochondrial Membranes
Mitochondria
Cytoplasm
Enzymes
Proteins

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Lysosomal chymotrypsin B potentiates apoptosis via cleavage of Bid. / Zhao, Kai; Zhao, Xingyu; Tu, Yaping; Miao, Qi; Cao, Dongxu; Duan, Wenjuan; Sun, Yang; Wang, Jincheng; Wei, Taotao; Yang, Fuyu.

In: Cellular and Molecular Life Sciences, Vol. 67, No. 15, 08.2010, p. 2665-2678.

Research output: Contribution to journalArticle

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, vol. 67, no. 15, pp. 2665-2678. https://doi.org/10.1007/s00018-010-0356-0
Zhao, Kai ; Zhao, Xingyu ; Tu, Yaping ; Miao, Qi ; Cao, Dongxu ; Duan, Wenjuan ; Sun, Yang ; Wang, Jincheng ; Wei, Taotao ; Yang, Fuyu. / Lysosomal chymotrypsin B potentiates apoptosis via cleavage of Bid. In: Cellular and Molecular Life Sciences. 2010 ; Vol. 67, No. 15. pp. 2665-2678.
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AU - Sun, Yang

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