calpain has been researched along with Carcinoma--Large-Cell* in 1 studies
1 other study(ies) available for calpain and Carcinoma--Large-Cell
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Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family members.
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. Topics: Apoptosis; Calcium; Calpain; Carcinoma, Large Cell; Cell Nucleus; Cell Separation; Cells, Cultured; Cytochrome c Group; Cytoplasm; DNA; Enzyme Activation; Flow Cytometry; Humans; Ionomycin; Ionophores; Lung Neoplasms; Mitochondria; Models, Molecular; Oligopeptides; Poly(ADP-ribose) Polymerases; Protein Binding; Proto-Oncogene Proteins c-bcl-2; Time Factors; Tumor Cells, Cultured | 2002 |