Participation of the conventional calpains in apoptosis

Tao Lu, Ying Xu, Maura T. Mericle, Ronald L. Mellgren

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

The conventional calpains, m- and μ-calpain, are suggested to be involved in apoptosis triggered by many different mechanisms. However, it has not been possible to definitively associate calpain function with apoptosis, largely because of the incomplete selectivity of the cell permeable calpain inhibitors used in previous studies. In the present study, Chinese hamster ovary (CHO) cell lines overexpressing μ-calpain or the highly specific calpain inhibitor protein, calpastatin, have been utilized to explore apoptosis signals that are influenced by calpain content. This approach allows unambiguous alteration of calpain activity in cells. Serum depletion, treatment with the endoplasmic reticulum (ER) calcium ATPase inhibitor thapsigargin, and treatment with calcium ionophore A23187 produced apoptosis in CHO cells, which was increased in calpain overexpressing cells and decreased by induced expression of calpastatin. Inhibition of calpain activity protected β-spectrin, but not α-spectrin, from proteolysis. The calpains seemed not to be involved in apoptosis triggered by a number of other treatments. Calpain protected against TNF-α induced apoptosis. In contrast to previous studies, we found no evidence that calpains proteolyze IκB-α in TNF-α-stimulated cells. These studies indicate that the conventional calpains participate in some, but not all, apoptotic signaling mechanisms. In most cases, they contributed to apoptosis, but in at least one case, they were protective.

Original languageEnglish (US)
Pages (from-to)16-26
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1590
Issue number1-3
DOIs
StatePublished - Jun 12 2002
Externally publishedYes

Keywords

  • A23187
  • Apoptosis
  • CHO cell
  • Calpain
  • TNF-alpha
  • Thapsigargin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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