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          Institute: MPI für Biochemie     Collection: Structure Research (R. Huber)     Display Documents



ID: 41719.0, MPI für Biochemie / Structure Research (R. Huber)
Lonomycin-activated calpain triggers apoptosis - A probable role for Bcl-2 family members
Authors:Gil-Parrado, S.; Fernandez-Montalvan, A.; Assfalg-Machleidt, I.; Popp, O.; Bestvater, F.; Holloschi, A.; Knoch, T. A.; Auerswald, E. A.; Welsh, K.; Reed, J. C.; Fritz, H.; Fuentes-Prior, P.; Spiess, E.; Salvesen, G. S.; Machleidt, W.
Language:English
Date of Publication (YYYY-MM-DD):2002-07-26
Title of Journal:Journal of Biological Chemistry
Journal Abbrev.:J. Biol. Chem.
Volume:277
Issue / Number:30
Start Page:27217
End Page:27226
Review Status:Peer-review
Audience:Not Specified
Abstract / Description: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.
Comment of the Author/Creator:Date: 2002, JUL 26
External Publication Status:published
Document Type:Article
Communicated by:N.N.
Affiliations:MPI für Biochemie/Structure Research (Huber)
External Affiliations:Univ Munich Klinikum, Klin Chem & Klin Biochem Abt, Chirurg; Klin Innenstadt, Nussbaumstr 20, D-80336 Munich, Germany; Univ Munich Klinikum, Klin Chem & Klin Biochem Abt, Chirurg Klin Innenstadt, D-80336 Munich, Germany; Univ Munich, Adolf Butenandt Inst, D-80336 Munich, Germany; Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany; Fachhsch Mannheim, Inst Molekularbiol & Zellkulturtech, D-68163 Mannheim, Germany; Burnham Inst, La Jolla, CA 92037 USA
Identifiers:ISI:000177055900067 [ID No:1]
ISSN:0021-9258 [ID No:2]
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