Granulocyte differentiation inducer, hexapeptide HLDF-6, decreases cytotoxic effect of tumor necrosis factor on HL-60 cell line.
The effect of hexapeptide HLDF-6, the granulocytic differentiation inducer, on the tumor necrosis factor alpha (TNF-alpha)-induced differentiation and apoptosis of human promyelocytic leukemia HL-60 cells has been investigated. Costimulation of HL-60 cells with HLDF-6 and TNF-alpha enhanced granulocyte differentiation, whereas the level of monocyte differentiation remained unchanged; however, the cytotoxic action of TNF-alpha on these cells decreased. The protective effect of HLDF-6 peptide did not depend on activation of NF-kappaB (nuclear transcription factor). Since HLDF-6 peptide decreases the number of cells entering apoptosis caused by C(2)-ceramide, a mediator of TNF-induced apoptosis, and also reduces TNF-alpha-mediated activation of caspase-3, we have proposed the hypothesis that HLDF-6 increases resistance of HL-60 cells to the TNF-alpha cytotoxic effect due to inhibition of some stages of mitochondria-dependent apoptotic signaling.
Gibanova
N V
NV
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
Rakitina
T V
TV
Lipkin
V M
VM
Kostanyan
I A
IA
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002454:Cell Differentiation; D002518:Ceramides / Q000494:pharmacology; D004347:Drug Interactions; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D009000:Monocytes / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002518:Ceramides; D016328:NF-kappa B; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C513648:threonyl-glycyl-glutamyl-asparaginyl-histidylarginine; D053148:Caspase 3; D053181:Caspase 8