Involvement of caspases in 4-hydroxy-alkenal-induced apoptosis in human leukemic cells

W. Zhang, Q. He, L. L. Chan, F. Zhou, M. El Naghy, E. B. Thompson, Naseem Ansari

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

4-Hydroxynonenal (HNE), a reactive and cytotoxic end-product of lipid peroxidation, has been suggested to be a key mediator of oxidative stress-induced cell death and in various cell types has been shown to induce apoptosis. We have demonstrated that HNE, at micromolar concentrations, induces dose- and time-dependent apoptosis in a leukemic cell line (CEM-C7). Interestingly, much higher concentrations of HNE (>15-fold) were required to induce apoptosis in leukocytes obtained from normal individuals. We also demonstrate that HNE causes a decrease in clonogenicity of CEM-C7 cells. Furthermore, our data characterize the caspase cascade involved in HNE-induced apoptosis in CEM-C7 cells. Using specific fluorogenic substrates and irreversible peptide inhibitors, we demonstrate that caspase 2, caspase 3, and caspase 8 are involved in HNE-induced apoptosis, and that caspase 2 is the first initiator caspase that activates the executioner caspase 3, either directly or via activation of caspase 8. Our studies also suggest the involvement of another executioner caspase, which appears to be similar to caspase 8 but not caspases 2 and 3, in its specificity. The demonstration of decreased clonogenicity by HNE in the leukemic cells, and their higher susceptibility to HNE-induced apoptosis as compared to the normal cells, suggests that such compounds may have potential for leukemia chemotherapy.

Original languageEnglish (US)
Pages (from-to)699-706
Number of pages8
JournalFree Radical Biology and Medicine
Volume30
Issue number6
DOIs
StatePublished - Mar 15 2001

Fingerprint

Caspases
Apoptosis
Caspase 2
Caspase 8
Caspase 3
Initiator Caspases
Oxidative stress
Chemotherapy
4-hydroxy-2-nonenal
Cell death
Fluorescent Dyes
Lipid Peroxidation
Leukemia
Oxidative Stress
Leukocytes
Cell Death
Demonstrations
Chemical activation
Cells
Lipids

Keywords

  • 4-Hydroxynonenal
  • Apoptosis
  • Caspases
  • Free radicals
  • Leukemia
  • Oxidative stress

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Involvement of caspases in 4-hydroxy-alkenal-induced apoptosis in human leukemic cells. / Zhang, W.; He, Q.; Chan, L. L.; Zhou, F.; El Naghy, M.; Thompson, E. B.; Ansari, Naseem.

In: Free Radical Biology and Medicine, Vol. 30, No. 6, 15.03.2001, p. 699-706.

Research output: Contribution to journalArticle

Zhang, W. ; He, Q. ; Chan, L. L. ; Zhou, F. ; El Naghy, M. ; Thompson, E. B. ; Ansari, Naseem. / Involvement of caspases in 4-hydroxy-alkenal-induced apoptosis in human leukemic cells. In: Free Radical Biology and Medicine. 2001 ; Vol. 30, No. 6. pp. 699-706.
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