J Korean Orthop Assoc.  2001 Aug;36(4):317-325.

The Signaling Pathway of G-protein Rac and Eicosanoid Synthesis by Titanium Particles

• Lee SS
• Her JY
• Woo CH
• Kim JH
• Chang JD

Abstract

PURPOSE
In order to understand the intracellular signaling pathway involving the c-fos gene expression that is caused by Titanium-particles, we analyzed the involvement of Rac, cytosolic phospholipase A2, and eicosanoids (e.g. leukotriene B4 and prostaglandin E2) as well as c-fos.
MATERIALS AND METHODS
We tested whether or not Titanium-particles activate a c-fos serum response element in Rat-2 fibroblasts. To measure the activity of the c-fos serum response element, we analyzed the serum response element using a luciferase reporter system. The luciferase activity was measured using a scintillation spectrophotometer. Next, we analyzed the involvement of Rac and the eicosanoid synthesis mechanisms which are downstream mediators of Rac in the c-fos serum response element activation cascade.
RESULTS
Titanium-particles cause an activation of the c-fos serum response element and this activation was selectively repressed by RacN17 and by pretreatment of the inhibitors of cytosolic phospholipase A2, cyclooxygenase or 5-lipoxygenase. Eicosanoid synthesis was increased in a Rac-dependent manner in response to the presence of Titanium- particles.
CONCLUSION
'Rac, a member of G-protein, which is involved in the eicosanoid synthesis' may play a critical role in the Titanium-induced signaling cascade. Thus, we speculated that the 'Rac-cytosolic phospholipase A2-eicosanoids-c-fos cascade' may be a possible mechanism that produces eicosanoid synthesis caused by Titanium-particles in the periprosthetic osteolytic process.

Keyword

Fibroblast; Titanium; Rac; Eicosanoid; c-fos

MeSH Terms

Arachidonate 5-Lipoxygenase
Cytosol
Eicosanoids
Fibroblasts
Genes, fos
GTP-Binding Proteins*
Leukotriene B4
Luciferases
Phospholipases
Phospholipases A2
Prostaglandin-Endoperoxide Synthases
Serum Response Element
Titanium*
Arachidonate 5-Lipoxygenase
Eicosanoids
GTP-Binding Proteins
Leukotriene B4
Luciferases
Phospholipases
Phospholipases A2
Prostaglandin-Endoperoxide Synthases
Titanium