Calpain activation is upstream of caspases in radiation-induced apoptosis (original) (raw)

• Original Paper
• Published: 01 December 1998
• Debra M Finucane3,
• Douglas R Green3,
• John S Elce4,
• Sharad Kumar5,
• Emad S Alnemri6,
• Gerald Litwack6,
• KumKum Khanna1,
• Martin F Lavin1,2 &
• …
• Dianne J Watters1

Cell Death & Differentiation volume 5, pages 1051–1061 (1998)Cite this article

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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.

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Authors and Affiliations

1. Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, P.O. Royal Brisbane Hospital, Herston, 4029, Queensland, Australia
   Nigel J Waterhouse, KumKum Khanna, Martin F Lavin & Dianne J Watters
2. Department of Surgery, University of Queensland, St. Lucia, 4072, Queensland, Australia
   Nigel J Waterhouse & Martin F Lavin
3. La Jolla Institute of Allergy and Immunology, 10355 Science Center Drive, San Diego, 92121, California, USA
   Debra M Finucane & Douglas R Green
4. Department of Biochemistry, Queen's University, Kingston, K7L 3N6, Ontario, Canada
   John S Elce
5. The Hanson Centre for Cancer Research, P.O. Box 14, Rundle Mall, Adelaide, 5000, South Australia, Australia
   Sharad Kumar
6. Department of Pharmacology and the Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania, USA
   Emad S Alnemri & Gerald Litwack

Authors

1. Nigel J Waterhouse
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2. Debra M Finucane
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3. Douglas R Green
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4. John S Elce
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5. Sharad Kumar
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6. Emad S Alnemri
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7. Gerald Litwack
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8. KumKum Khanna
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9. Martin F Lavin
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10. Dianne J Watters
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Correspondence toDianne J Watters.

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Edited by S.J. Martin

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Waterhouse, N., Finucane, D., Green, D. et al. Calpain activation is upstream of caspases in radiation-induced apoptosis.Cell Death Differ 5, 1051–1061 (1998). https://doi.org/10.1038/sj.cdd.4400425

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• Received: 09 March 1998
• Revised: 14 May 1998
• Accepted: 02 June 1998
• Published: 01 December 1998
• Issue Date: 01 December 1998
• DOI: https://doi.org/10.1038/sj.cdd.4400425

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