The Signaling Pathway of G-protein Rac and Eicosanoid Synthesis by Titanium Particles.
- Author:
Sang Soo LEE
1
;
Jae Young HER
;
Chang Hoon WOO
;
Jae Hong KIM
;
Jun Dong CHANG
Author Information
1. Department of Orthopaedic Surgery, Pohang St. Mary's Hospital, Pohang, Korea.
- Publication Type:Original Article
- Keywords:
Fibroblast;
Titanium;
Rac;
Eicosanoid;
c-fos
- MeSH:
Arachidonate 5-Lipoxygenase;
Cytosol;
Eicosanoids;
Fibroblasts;
Genes, fos;
GTP-Binding Proteins*;
Leukotriene B4;
Luciferases;
Phospholipases;
Phospholipases A2;
Prostaglandin-Endoperoxide Synthases;
Serum Response Element;
Titanium*
- From:The Journal of the Korean Orthopaedic Association
2001;36(4):317-325
- CountryRepublic of Korea
- Language:Korean
-
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.
