Role of Phosphoinositide 3-Kinase and Extracellular Signal-Regulated Kinase Pathways in Granulocyte Macrophage-Colony-Stimulating Factor Failure to Delay Fas-Induced Neutrophil Apoptosis in Elderly Humans
| Autor: | Salvatore Antonaci, Cosimo Tortorella, Giuseppina Piazzolla, Valentina Cappiello, Isabella Stella, Olivia Simone |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Aging Fas Ligand Protein Cell Survival Neutrophils Receptor expression Apoptosis Suppressor of Cytokine Signaling Proteins Biology Suppressor of Cytokine Signaling 1 Protein Humans SOCS3 Phosphorylation Extracellular Signal-Regulated MAP Kinases Protein kinase B Cells Cultured PI3K/AKT/mTOR pathway Aged Phosphoinositide-3 Kinase Inhibitors Aged 80 and over Flavonoids Phosphoinositide 3-kinase Kinase Antibodies Monoclonal Granulocyte-Macrophage Colony-Stimulating Factor Cell biology Receptors Granulocyte-Macrophage Colony-Stimulating Factor Suppressor of Cytokine Signaling 3 Protein Case-Control Studies biology.protein Female Geriatrics and Gerontology Signal transduction |
| Zdroj: | The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 61:1111-1118 |
| ISSN: | 1758-535X 1079-5006 |
| DOI: | 10.1093/gerona/61.11.1111 |
| Popis: | Fas-stimulated neutrophils from elderly individuals show impaired granulocyte macrophage-colony-stimulating factor (GM-CSF)-induced apoptosis cell rescue. Herein, this defect was found to be associated with a significant reduction in GM-CSF-mediated Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Using Akt and ERK1/2 inhibitors, we demonstrated that both kinases were critical for GM-CSF antiapoptotic effects. Whereas Akt inhibition also affected GM-CSF-dependent ERK1/2 phosphorylation, ERK1/2 inhibition did not affect GM-CSF-induced Akt phosphorylation, suggesting that phosphoinositide 3-kinase (PI3-K)/Akt and ERK1/2 are activated in series and that PI3-K is located upstream of ERK1/2 along the GM-CSF-dependent signaling pathway. No age-associated changes in GM-CSF receptor expression were observed. Interestingly, both suppressors of cytokine signaling (SOCS)1 and SOCS3 proteins were significantly higher in unstimulated neutrophils from elderly individuals and, unlike in young individuals, did not further increase following GM-CSF cell triggering. These results indicate that defective PI3-K/Akt/ERK1/2 activation, likely dependent on elevated SOCS1 and SOCS3 levels, may affect the GM-CSF capacity to delay neutrophil apoptosis in elderly persons. |
| Databáze: | OpenAIRE |
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