Differential involvement of caspases in hydroquinone-induced apoptosis in human leukemic HL-60 and Jurkat cells

Salmaan H. Inayat-Hussain, Shannon L. Winski, David Ross

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The benzene metabolite hydroquinone (HQ) is postulated to exert its myelotoxicity by bioactivation to reactive quinone derivatives in myeloperoxidase (MPO)-containing cells. In this study, the role of caspases in hydroquinone-induced apoptosis in MPO-rich HL-60 promyelocytic leukemia and MPO-deficient Jurkat T-lymphoblastic leukemia cells was investigated. HQ-induced apoptosis in both cell types was accompanied by phosphatidylserine (PS) exposure, caspases-3/-7 activation, PARP cleavage, DNA fragmentation, and ultrastructural changes as assessed by electron microscopy. In HL-60 cells, the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) blocked activation of caspases-3/-7, cleavage of PARP, and DNA, but PS externalization and cytoplasmic changes were not significantly affected. In marked contrast, all features of apoptosis were completely inhibited by Z-VAD.FMK in HQ-treated Jurkat cells. These data provide evidence for Z-VAD.FMK-insensitive and caspases-3/-7-independent pathway(s) in the externalization of PS and cytoplasmic changes during HQ-induced apoptosis in HL-60 cells. In contrast, in Jurkat cells, all of these changes required caspase activation. The ability of HQ to induce equivalent apoptosis in both MPO-deficient Jurkat cells and MPO-rich HL-60 cells demonstrates that MPO-catalyzed bioactivation of HQ is not a prerequisite for toxicity. The differential mechanisms of apoptosis in HL-60 and Jurkat T cells may reflect the MPO activity of these cells and, as a result, the amount of reactive BQ and other metabolites that are generated.

Original languageEnglish
Pages (from-to)95-103
Number of pages9
JournalToxicology and Applied Pharmacology
Volume175
Issue number2
DOIs
Publication statusPublished - 1 Sep 2001
Externally publishedYes

Fingerprint

Jurkat Cells
HL-60 Cells
Caspases
Peroxidase
Apoptosis
Caspase 7
Phosphatidylserines
Caspase 3
Chemical activation
Metabolites
T-Cell Leukemia
DNA Cleavage
Caspase Inhibitors
T-cells
DNA
DNA Fragmentation
hydroquinone
Benzene
Ketones
Precursor Cell Lymphoblastic Leukemia-Lymphoma

Keywords

  • Apoptosis
  • Benzene
  • Caspases
  • Hydroquinone
  • Myeloperoxidase
  • Phosphatidylserine exposure

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Differential involvement of caspases in hydroquinone-induced apoptosis in human leukemic HL-60 and Jurkat cells. / Inayat-Hussain, Salmaan H.; Winski, Shannon L.; Ross, David.

In: Toxicology and Applied Pharmacology, Vol. 175, No. 2, 01.09.2001, p. 95-103.

Research output: Contribution to journalArticle

Inayat-Hussain, Salmaan H. ; Winski, Shannon L. ; Ross, David. / Differential involvement of caspases in hydroquinone-induced apoptosis in human leukemic HL-60 and Jurkat cells. In: Toxicology and Applied Pharmacology. 2001 ; Vol. 175, No. 2. pp. 95-103.
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