A critical role of redox state in determining HL-60 cell granulocytic differentiation and apoptosis via involvement of PKC and NF-kappaB

The modifications of intracellular redox balance leads to important cellular changes in many cell types. Here, a causal relationship among redox state, granulocytic differentiation induced by all-trans retinoic acid (RA) or dibutyryl cAMP (dbcAMP) and apoptosis have been studied in the human acute p...

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Bibliographic Details
Published in:In vitro cellular & developmental biology. Animal 2010-06, Vol.46 (6), p.547-559
Main Authors: Savickiene, Jurate, Treigyte, Grazina, Gineitis, Arunas, Navakauskiene, Ruta
Format: Article
Language:English
Subjects:
Acetylcysteine - pharmacology
Apoptosis
Cell Differentiation
Granulocytes - cytology
Granulocytes - metabolism
HL-60 Cells
Humans
NF-kappa B - metabolism
Oxidation-Reduction
Protein Kinase C - metabolism
Signal Transduction
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Summary:The modifications of intracellular redox balance leads to important cellular changes in many cell types. Here, a causal relationship among redox state, granulocytic differentiation induced by all-trans retinoic acid (RA) or dibutyryl cAMP (dbcAMP) and apoptosis have been studied in the human acute promyelocytic leukaemia HL-60 cells. The modulation of intracellular reactive oxygen species levels by D: , L: -buthionine-(S, R) sulfoximide (BSO), and N: -acetyl-L: -cysteine (NAC) caused inducer- and time-dependent or stage-specific effects on HL-60 cell growth inhibition, differentiation and subsequent apoptosis. The presence of BSO during the commitment stage suppressed RA-but not dbcAMP-mediated differentiation, while NAC inhibited both. BSO alone and in combination with RA or dbcAMP-induced apoptosis, which was prevented by NAC in dbcAMP-but not in RA-treated cells. Using protein kinase C inhibitor, calphostin C, cross-talk effects between the intracellular redox state and PKC signalling was identified by demonstrating inducer-dependent changes in cell differentiation or apoptosis, which were associated with the changes in DNA-NF-kappaB binding activity. These observations suggest a critical role of redox state in determining HL-60 cell behaviour and provide new insights into the complex effects of redox perturbations on the intracellular signalling network via the involvement of PKC and NF-kappaB.
ISSN:1543-706X
DOI:10.1007/s11626-010-9296-0