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  Lonomycin-activated calpain triggers apoptosis - A probable role for Bcl-2 family members

Gil-Parrado, S., Fernandez-Montalvan, A., Assfalg-Machleidt, I., Popp, O., Bestvater, F., Holloschi, A., et al. (2002). Lonomycin-activated calpain triggers apoptosis - A probable role for Bcl-2 family members. Journal of Biological Chemistry, 277(30), 27217-27226.

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Genre: Journal Article
Alternative Title : J. Biol. Chem.

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 Creators:
Gil-Parrado, S., Author
Fernandez-Montalvan, A., Author
Assfalg-Machleidt, I.1, Author              
Popp, O., Author
Bestvater, F., Author
Holloschi, A., Author
Knoch, T. A., Author
Auerswald, E. A., Author
Welsh, K., Author
Reed, J. C., Author
Fritz, H., Author
Fuentes-Prior, P.2, Author              
Spiess, E., Author
Salvesen, G. S., Author
Machleidt, W.1, Author              
Affiliations:
1External Organizations, ou_persistent22              
2Huber, Robert / Structure Research, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565155              

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 Abstract: Ubiquitous calpains (mu- and m-calpain) have been repeatedly implicated in apoptosis, but the underlying mechanism(s) remain(s) to be elucidated. We examined ionomycin-induced cell death in LCLC 103H cells, derived from a human large cell lung carcinoma. We detected hallmarks of apoptosis such as membrane blebbing, nuclear condensation, DNA ladder formation, caspase activation, and poly-(ADP-ribose)polymerase cleavage. Apoptosis was prevented by preincubation of the cells with the calpain inhibitor acetyl-calpastatin 27-peptide and the caspase inhibitor Z-DEVD-fmk, implicating both the calpains and caspases in the apoptotic process. The apoptotic events correlated in a calpastatin-inhibitable manner with Bid and Bcl-2 decrease and with activation of caspases-9, -3, and -7. In vitro both ubiquitous calpains cleaved recombinant Bcl-2, Bid, and Bcl-X-L at single sites truncating their N-terminal regions. Binding studies revealed diminished interactions of calpain-truncated Bcl-2 and Bid with immobilized intact Bcl-2 family proteins. Moreover, calpain-cleaved Bcl-2 and Bid induced cytochrome c release from isolated mitochondria. We conclude that ionomycin-induced calpain activation promotes decrease of Bcl-2 proteins thereby triggering the intrinsic apoptotic pathway.

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Language(s): eng - English
 Dates: 2002-07-26
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 41719
ISI: 000177055900067
 Degree: -

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Title: Journal of Biological Chemistry
  Alternative Title : J. Biol. Chem.
Source Genre: Journal
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Pages: - Volume / Issue: 277 (30) Sequence Number: - Start / End Page: 27217 - 27226 Identifier: ISSN: 0021-9258