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 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.
Department of Developmental Biology, Institute of Biochemistry, Mokslininku st. 12, 08662, Vilnius, Lithuania.
Jurate
J
Savickiene
Grazina
G
Treigyte
Arunas
A
Gineitis
Ruta
R
Navakauskiene
D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis; D002454:Cell Differentiation; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction
D016328:NF-kappa B; D011493:Protein Kinase C; D000111:Acetylcysteine