Antiapoptotic effect of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and cyclic AMP on human neutrophils: protein synthesis-dependent and protein synthesis-independent mechanisms and the role of the Janus kinase-STAT pathway
Autor: | Chikahiko Sakamoto, Seiichi Kitagawa, Taro Hasegawa, Fumihiko Hato, Kenichi Suzuki, Mika Akahori, Masayuki Hino |
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Rok vydání: | 2003 |
Předmět: |
Adenosine monophosphate
STAT3 Transcription Factor Transcription Genetic Neutrophils Apoptosis Biology Cycloheximide Granulocyte chemistry.chemical_compound Proto-Oncogene Proteins Granulocyte Colony-Stimulating Factor medicine STAT5 Transcription Factor Humans Enzyme Inhibitors Phosphorylation STAT3 STAT5 JAK-STAT signaling pathway Granulocyte-Macrophage Colony-Stimulating Factor Hematology Janus Kinase 2 Protein-Tyrosine Kinases Milk Proteins Molecular biology DNA-Binding Proteins medicine.anatomical_structure chemistry Bucladesine Protein Biosynthesis STAT protein biology.protein Trans-Activators Janus kinase Signal Transduction |
Zdroj: | International journal of hematology. 77(1) |
ISSN: | 0925-5710 |
Popis: | Spontaneous neutrophil apoptosis during culture was delayed by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), or dibutyryl-cyclic adenosine monophosphate (cAMP), whereas apoptosis was accelerated by cycloheximide or actinomycin D. G-CSF-mediated antiapoptosis was completely abolished by cycloheximide or actinomycin D, whereas GM-CSF-mediated antiapoptosis was not completely abolished by these inhibitors. Antiapoptosis induced by dibutyryl-cAMP was highly resistant to cycloheximide, and that induced by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone was unaffected by cycloheximide. G-CSF- and GM-CSF-mediated antiapoptosis and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and STAT5 were inhibited by AG490, an inhibitor of Janus kinase. The level of Mcl-1 protein was not associated with neutrophil apoptosis. The results suggest that (a) neutrophil survival in the resting state is primarily regulated by the constitutive synthesis of antiapoptotic proteins; (b) the prevention of spontaneous apoptosis is mediated through the protein synthesis-dependent and/or protein synthesis-independent mechanisms according to the stimuli used; and (c) the Janus kinase-STAT pathway is involved in G-CSF- and GM-CSF-mediated antiapoptosis. |
Databáze: | OpenAIRE |
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