Abstract |
Overgrowth of rheumatoid synoviocytes, which results in joint destruction, is due to impaired balance between cell proliferation and cell death (apoptosis). Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. We investigated the effects of ceramide on growth-promoting anti-apoptotic signals in rheumatoid synovial cells. Human synovial cells isolated from patients with rheumatoid arthritis (RA) were stimulated with platelet-derived growth factor (PDGF) in the presence or absence of C2-ceramide. The kinase activity of Akt, MEK, and ERK1/2 was analyzed in PDGF-stimulated synovial cells by Western blot analysis. Pretreatment with C2-ceramide completely inhibited PDGF-induced cell cycle progression of rheumatoid synovial cells. PDGF stimulation induced phosphorylation and activation of Akt, MEK, and ERK1/2 in rheumatoid synovial cells. C2-ceramide inhibited the activation of Akt, MEK and ERK1/2 in PDGF-stimulated synovial cells. Our data demonstrated that inhibition of anti-apoptotic kinases, such as Akt and ERK1/2, may play an important role in ceramide-mediated apoptosis of rheumatoid synovial cells.
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Authors | K Migita, S Honda, S Yamasaki, Y Hirai, T Fukuda, T Aoyagi, M Kita, H Ida, T Tsukada, A Kawakami, Y Kawabe, K Eguchi |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 269
Issue 1
Pg. 70-5
(Mar 05 2000)
ISSN: 0006-291X [Print] United States |
PMID | 10694479
(Publication Type: Journal Article)
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Copyright | Copyright 2000 Academic Press. |
Chemical References |
- N-acetylsphingosine
- Platelet-Derived Growth Factor
- Proto-Oncogene Proteins
- Protein Kinases
- AKT1 protein, human
- Protein Serine-Threonine Kinases
- Proto-Oncogene Proteins c-akt
- Mitogen-Activated Protein Kinases
- MAP Kinase Kinase Kinases
- Sphingosine
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Topics |
- Apoptosis
(drug effects)
- Arthritis, Rheumatoid
(pathology)
- Cell Division
(drug effects)
- Cells, Cultured
- Enzyme Activation
(drug effects)
- Humans
- MAP Kinase Kinase Kinases
(metabolism)
- Mitogen-Activated Protein Kinases
(metabolism)
- Platelet-Derived Growth Factor
(pharmacology)
- Protein Kinases
(metabolism)
- Protein Serine-Threonine Kinases
- Proto-Oncogene Proteins
(metabolism)
- Proto-Oncogene Proteins c-akt
- Signal Transduction
- Sphingosine
(analogs & derivatives, pharmacology)
- Synovial Membrane
(drug effects, pathology)
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