Mechanism of β2- microglobulin-induced apoptosis in the K562 leukemia cell line, defective in major histocompatibility class 1

Ching Huang Wu, John D. Gordon, Xiaoling Zhong, Ahmad R. Safa

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: It has been shown that exogenous β2-microglobulin (β2m) triggers significant apoptosis in several cell lines, but the molecular mechanism of β2m-induced apoptosis remains to be found. Materials and Methods: To understand the mechanism of β2m-induced apoptosis, we added purified human β2m to cultures of K562 human chronic myelocytic leukemia cells, detected apoptosis by DNA fragmentation and annexin V binding assays, measured mitochondrial membrane potential (Δψm), and used Z-VAD-fmk, a general inhibitor of caspases, inhibitors of caspases-1 and-3, as well as Western blot analysis to detect activated caspases. Results: β2m-induced apoptosis was associated with decreased ΔΨm K562 cells. Treatment With the general caspase inhibitor Z-VAD-fmk, as well as the caspase-1 inhibitor YVAD-CHO, significantly blocked β2m-induced apoptosis. However, Western blot analysis revealed that caspase-1 was intrinsically activated in untreated as well as β2m-treated K562 cells. Furthermore, β2m-induced apoptosis was not associated with the cleavage of caspase-3 as revealed by Western blot analysis, but was inhibited by an inhibitor of caspase-3, Z-DEVD-CHO, suggesting that not caspase-3, but a caspase-3-like enzyme may be involved in β2m-induced apoptosis. Western blot analysis also revealed that caspases-4, -8 and -9 were not activated during β2m-induced apoptosis in these cells. Conclusion: These results reveal that β2m-induced apoptosis in K562 cells occurs by a mechanism dependent on decreased mitochondrial Δψm. Moreover, while caspase-1 activity may be one of the factors involved in β2m-induced apoptosis, activation of this caspase alone does not cause apoptosis, and other proapoptotic factors including activation of a caspase-3-like enzyme, independently of caspases-4, -8 and -9 activity, may be required to trigger apoptosis.

Original languageEnglish (US)
Pages (from-to)2613-2621
Number of pages9
JournalAnticancer Research
Volume22
Issue number5
StatePublished - Sep 1 2002

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Keywords

  • β-Microglobulin
  • Apoptosis
  • Caspases
  • cytochrome c
  • Leukemia
  • Mitochondria

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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