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- Title
Calpain activation is upstream of caspases in radiation-induced apoptosis.
- Authors
Waterhouse, Nigel J; Finucane, Debra M; Green, Douglas R; Elce, John S; Kumar, Sharad; Alnemri, Emad S; Litwack, Gerald; Khanna, KumKum; Lavin, Martin F; Watters, Dianne J
- Abstract
The molecular events involved in apoptosis induced by ionizing radiation remain unresolved. In this paper we show that the cleavage of fodrin to a 150 kDa fragment is an early proteolytic event in radiation-induced apoptosis in the Burkitts' Lymphoma cell line BL30A and requires 100 µM zVAD-fmk for inhibition. Caspases-1, -3, -6 and -7 were shown to cleave fodrin to the 150 kDa fragment in vitro and all were inhibited by 10 µM zVAD-fmk. We also show that the in vitro cleavage of fodrin by calpain is inhibited by 100 µM zVAD-fmk as was the calpain-mediated hydrolysis of casein. We demonstrate that calpain is activated within 15 min after radiation exposure, concomitant with the cleavage of fodrin to the 150 kDa fragment whereas caspase-3 is activated at 2 h correlating with the cleavage of fodrin to the 120 kDa fragment. These results support a role for calpain in the early phases of the radiation-induced apoptosis pathway, upstream of the caspases.
- Subjects
APOPTOSIS; IONIZING radiation; BURKITT'S lymphoma
- Publication
Cell Death & Differentiation, 1998, Vol 5, Issue 12, p1051
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/sj.cdd.4400425