Elucidation of the mechanism of action of vitamin E as an antiosteoporotic agent via proteomics approach

Abstract

Osteoporosis is a chronic and progressive disease of multifactorial etiology and is the most common metabolic bone disease in the United States and the world at large. The prevalence of osteoporosis in Malaysia was reported as 24% in 2005, the hip fracture rate apparently as a result of osteoporosis is approximately 0.9 per 1000 persons over 50 years. Various cells, cytokines, mediators and numerous signaling pathways as well as genetic and environmental factors play role in bone remodeling process. Palm tocotrienol enrich fraction (PVE) and alpha-tocopherol (ATF) have been reported to prevent the increase in interleukin-1 (IL-1) and interleukin-6 (IL-6) in ovariectomised rats and increase osteoblastic bone formation relative to osteoclastic bone resorption, resulting in positive bone remodeling. In this study, female rats were divided into 4 groups N=10 : ovariectomised (OVX), sham-operated (SO), ovariectomised supplemented with Palm tocotrienol enrich fraction (PVE) and ovariectomised supplemented with alpha tocopherol (ATF). OVX and SO group was treated with 0.4ml olive oil, PVE group was treated with 0.4ml 60mg/kg of Palm tocotrienol enrich fraction while ATF was treated with 0.4ml 60mg/kg of alpha-tocopherol. All treatment was carried out 6 days per week for 2 months via oral gavage. Two dimensional gel electrophoresis (2-DE) and mass spectrometer (Proteomics technique) were used to analyze the differential protein expression in femoral and humeri bones. The isoelectric point (pI) and molecular weight (MW) of the identified proteins correspond to protein homologous glyceraldehyde-3-phosphate dehydrogenase, Eno3 Beta-Enolase, Vimentin, Ubr 2 Protein, Sema 3A, Tropomyosin , Annexin A1, Hemoglobin subunit alpha, Myh7 Myosin-7 while seven of the protein spots did not match any protein using the program MASCOT. Supplementation of PVE and ATF caused the expression of heat shock, antioxidant, anti-inflammatory and bone formation proteins. Anti-osteoporotic effect of PVE and ATF may be due to the modulation of these proteins which helps to protect the bone and enhance bone formation.