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

• Published in: In vitro cellular & developmental biology. Animal 2011-01, Vol.47 (1), p.547-559
• Main Authors: Savickiene, Jurate, Treigyte, Grazina, Gineitis, Arunas, Navakauskiene, Ruta
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Apoptosis; Cyclic AMP; Differentiation; Intracellular signalling; N-Acetyl-L-cysteine; Protein kinase C; Reactive oxygen species; Redox properties; Retinoic acid
• ISSN: 1071-2690
• DOI: 10.1007/s11626-010-9296-0

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- Delta *kB 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- Delta *kB.