Ceramide-induced nuclear translocation of NF-kappa B is a potential mediator of the apoptotic response to TNF-alpha in murine clonal osteoblasts.

Abstract

Osteoblasts are affected by TNF-alpha overproduction by immune cells during inflammation. We demonstrate that apoptosis is induced in murine osteoblastic MC3T3-E1 cells by exceeding the concentrations 100 units/mL of TNF-alpha and 10 mumol/L of synthetic ceramide. The apoptotic signaling pathway activated by TNF-alpha was examined in MC3T3-E1 cells. Endogenous cellular ceramide concentrations increased within 3 min, and comparable peak levels were observed for 30 min after TNF-alpha treatment. Activation of nuclear factor-kappa B (NF-kappa B) was detected after TNF-alpha or synthetic ceramide stimulation. The concentration of NF-kappa B increased in the perinuclear region after 5 min of treatment and translocation into the nucleus was observed within 15 min of treatment. Degradation of I kappa B alpha/MAD-3 was observed after 60 min of ceramide treatment. These results indicate that nuclear translocation and activation of NF-kappa B through TNF-alpha generated ceramide may be one important apoptotic signaling pathway in MC3T3-E1 cells. The osteoblastic apoptosis triggered by TNF-alpha-generated ceramide may explain the inhibition of bone formation during severe bone inflammation.

• Authors: I Kitajima, Y Soejima, I Takasaki, H Beppu, T Tokioka, I Maruyama
• Journal: Bone (Bone) Vol. 19 Issue 3 Pg. 263-70 (Sep 1996) ISSN: 8756-3282 [Print] United States
• PMID: 8873967 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ceramides
• DNA-Binding Proteins
• I-kappa B Proteins
• NF-kappa B
• Nfkbia protein, mouse
• Nuclear Proteins
• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• NF-KappaB Inhibitor alpha

Topics

• Animals
• Apoptosis (drug effects)
• Cell Nucleus (drug effects, metabolism)
• Ceramides (pharmacology)
• Clone Cells (drug effects)
• DNA-Binding Proteins (metabolism)
• I-kappa B Proteins
• Mice
• NF-KappaB Inhibitor alpha
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nuclear Proteins (metabolism)
• Osteoblasts (drug effects, metabolism, ultrastructure)
• Recombinant Proteins (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)