Bone Proteome Study in Ovariectomised Rats Supplemented with Palm Vitamin E
Supplementation of palm vitamin E has been reported
to prevent loss of bone density in ovariectomised female rats. The
mechanism by which palm vitamin E exerts these effects is still
unknown. We hypothesized that palm vitamin E may act by
preventing the protein expression changes. Two dimensional poly
acyrilamide gel electrophoresis (2-D PAGE) and PD Quest software
genomic solutions Investigator (proteomics) was used to analyze the
differential protein expression profile in femoral and humeri bones
harvested from three groups of rats; sham-operated rats (SO),
ovariectomised rats (Ovx) and ovariectomised rats supplemented for
2 months with palm vitamin E. The results showed that there were
over 300 valued spot on each of the groups PVE and OVX as
compared to about 200 in SO. Comparison between the differential
protein expression between OVX and PVE groups showed that ten
spots were down –regulated in OVX but up-regulated in PVE. The
ten differential spots were separately named P1-P10. The
identification and understanding of the pathway of the differential
protein expression among the groups is ongoing and may account for
the molecular mechanism through which palm vitamin E exert its
anti-osteoporotic effect.
[1] Michaëlsson,K., Melhus,H., Ferm,H., 2005. Genetic liability to
fractures in the elderly Arch. Intern. Med. 165:1825-1830.
[2] Slemenda, C.W., Christian,J.C., Williams,C.J. et al., 1991. Genetic
determinants of bone mass in adult women: a reevaluation of the twin
model and the potential importance of gene interaction on heritability
estimates" J. Bone Miner. Res. 6:561-567.
[3] Pooneh, S. and Mohammad, A. 2011. A comprehensive review of the
shared roles of inflammatory cytokines in osteoporosis and
cardiovascular disease as two common old people problem; actions
towards development of new drugs" International Journal of
Pharmacology 7(5): 552-567.
[4] Kong,Y.Y., Feige,U., Sarosi, Iet al., 1999. Activated T cells regulate
bone loss and joint destruction in adjuvant arthritis through
osteoprotegerin ligand" Nature 402:304-309.
[5] Manolagas, S.C., 2000. Birth and death of bone cells: Basic regulatory
mechanism and implications for the pathogenesis and treatment of
osteoporosis" Endocrinol.Rev., 21: 115-137.
[6] Goa,Y., Grassi, F, Robbie,M, Terauchi,M et al., 2007. IFN-╬│ stimulates
osteoclast formation and bone loss in vivo via antigen-driven T cell
activation" J.Clin Invest., 117:122-132.
[7] Miyaura,C., Kusano,K., Masuzawa,T., et al., 1995. Endogenous boneresorbing
factors in estrogen deficiency: Cooperative effects of IL-1 and
IL-6 J.Bone. Miner.Res., 10: 1365-1373.
[8] De Martins, M., Di Benedetto,M.C., Mengoli L.P., et al., 2006. Senile
osteoporosis: Is it an immune-mediated disease" Inflamm. Res., 55: 399-
404.
[9] Lacativa,P.G. and Farias, M.L, 2010. Osteoporosis and inflammatory
Arq. Bras. Endocrinol Metab., 54:123-132.
[10] Roggia,C. Gao,Y., Cenci, S., Weitzmann, M.N et al 2001. Upregulation
of TNF producing T cells in the bone marrow: A key
mechanism by which estrogen deficiency induces bone loss in vivo.
Proc. Natl.Acad.Sci. USA, 98: 13960-13965.
[11] Cenci,S. Toraldo,G., Weitzmann,M.N., Roggia C. et al., 2003.
Estrogen deficiency induces bone loss by increasing T cell proliferation
and life span through IFN-gamma-induced class II transactivator"
Proc.Natl.Acad. Sci USA., 100: 10405-10410.
[12] Serbinova,E.A. 1991. Alpha Tocotrienol Is A More Powerful membrane
Antioxidant Than Alpha Tocopherol", Oxid Damage Repair;77-81.
[13] Norazlina,M., Ling,H.L.R., Ima-Nirwana , S. et al., 2002. The effect of
vitamin E or calcium supplementation on bone mineral composition in
vitamin E deficient rats" Malaysia J. Biochem. Biol., 7: 1-5.
[14] Norazlina, M., Ima-Nirwana, S., Abd Gapor, M.T et al., 2002.
Tocotrienols are needed for normal bone calcification in growing female
rats. Asia Pacific J. Clin. Nutr., 11: 194-199.
[15] Norazlina, M., Ima-Nirwana, S., Gapor ,M.T., et al. 2000. Palm vitamin
E is comparable to alpha - tocopherol in maintaining bone mineral
density in ovariectomised female rats, Exp. Clin. Endocrinol. Diab.,
108: 305-310.
[16] Ima-Nirwana,S., Kiftiah, A., Sariza,T., Gapor,M.T., et al., 1999. Palm
vitamin E improves bone metabolism and survival rate in thyrotoxic rats.
Gen. Pharm., 32: 621-626.
[17] Nazrun, A.S., Norazlina,M., Norliza ,M., et al.2011. Tocotrienols as an
Anti-Osteoporotic Agent: The Progress So Far." International Journal of
Osteoporosis and Metabolic Disorders, 4: 1-14.
[18] Asmadi, A.Y.,Adam,A., Wan Ngah,W.Z., et al 2005. Tocotrienols and
╬▒- Tocopherol reduced acute and chronic lung lipid peroxidation
induced by paraquat in rats. Pak. J. Nutr., 4: 97-100.
[19] Nur Azlina,M.F., Nafeeza,M.I., Khalid , B.A.K. et al 2005. Effect of
tocotrienol on lipid peroxidation in experimental gastritis induced by
restraint stress. Pak. J. Nutr 4: 69-72 .
[20] Fan, Y. Liu, J., Wang,S. et al 2005.Functional proteome of bones in
rats with osteoporosis following ovariectomy. Life Sciences 76 :2893-
2901.
[21] Shen, S.H. Jing, Y.X. . Kuang , T.Y et al., 2003. Proteomics approach
to identify wound-response related proteins from rice leaf sheath.
Proteomics 3, 527-535.
[22] Mosekilde, L.and Mosekilde,L., et a 1990. Sex-difference in age-related
changes in vertebral body size, density and biomechanical competence
in normal individuals. Bone 11: 67-73.
[23] Kalu, D.N. 1991. The ovariectomised rat model of postmenopausal bone
loss. Bone Miner., 15: 175-191.
[24] Ima-Nirwana S., Norazlina, M.. Khali B.A.K d, et al 1998. Pattern of
bone mineral density in growing male and female rats gonadectomy. J.
Asean. Fed. Endoc. Soc 16: 21-26.
[25] Sack, M.N. Rader , D.J. Cannon R.O, et al 1994. Oestrogen and
inhibition of oxidation of low-density lipoproteins in postmenopausal
women" Lancet 343:269-270.
[26] Basu, S., Michaelsson,K., Olofsson,H., et al 2001. Association
between oxidative stress and bone mineral density" Biochem. Biophys.
Res. Commun., 288: 275-279.
[27] Badeau,M. Adlercreutz,H., Kaihovara,P., et al 2005. Estrogen A-ring
structure and antioxidant effect on lipoproteins. J. Steroid Biochem.
Mol. Biol,. 96: 271-278.
[28] Maggio,D., Barabani,M., Pierandrei,M., Polidori, M.C., et al 2003.
Marked decrease in plasma antioxidant in aged osteoporotic women:
Results of a cross-sectional study. J. Clin Endo, Metab., 88: 1523-1527
2003.
[29] Lean, J.M., Jagger, C.J. Kirsten, B. Fuller K., et al 2005. Hydrogen
peroxide is essential for estrogen-deficiency bone loss and osteoclast
formation. Endocrinol, 146: 728-735.
[30] Ahmad, N.S. Khalid, B.A.K., Luke, D.A. , et al. 2005. Tocotrienol
offers better protection than tocopherol from free radical-induced
damage of rat bone" Clin. Exp. Pharm. Physiol., 32: 761-770.
[31] Norazlina, M., Lukman, H.I, Nazrun A.S. , et al., 2007. Effects of
vitamin E supplementation on bone metabolism in nicotine-treated rats
Singapore Med. J. 48: 195-199.
[32] Hammer C.T and Wills E.D 1978. The role of lipid components of the
diet in the regulation of the fatty acid composition of the rat liver
endoplasmic reticulum and lipid peroxidation" Biochem. J., 174: 585-
595.
[33] Maniam, S. N. Mohamed,N. Shuid , A.N. et al., 2008. Palm tocotrienol
exerted better antioxidant activities in bone than alpha-tocopherol. Basic
Clin . Pharmacol.Toxicol., 103: 55-60.
[34] Wilkins, M. R., Pasquali, C., Appel, R. D., et al ".1996. From proteins to
proteomes: large scale protein identification by two-dimensional
electrophoresis and amino acid analysis." Biotechnology 14, 61-65.
[35] Kim, S. H. Jun, S. Hee-Sun, J. Sung-Kil, Let al 2005. Identification of
parathyroid hormone-regulated proteins in mouse bone marrow cells by
proteomics" Biochemical and Biophysical Research Communications
330 423-429.
[36] Chapam,C.M, Beilby, J.P., Humphries,S.E., et al 2003. Association of
an allelic variant of interleukin-6 with subclinical carotid atherosclerosis
in an Australian Community population" Eur. Heart. J., 24: 1494-1499,
2003.
[37] Manolagas S.G.and Jilka R.L. 1995. Mechanisms of disease: Bone
marrow, cytokines and bone remodeling- emerging insights into the
pathophysiology of osteoporosis" N. Engl. J. Med, 332:305-311.
[38] Scheidt-Nave,C. Bismar,H., Leidig-Bruckner,G. et al 2001. Serum
interleukin 6 is a major predictor of bone loss in women specific to the
first decade past menopause. J. Clin. Endocrinol Metab., 86: 2032-2042.
[39] Berton, B.E. 1996. The biological effects of interleukin 6" Med.Res.
Rev., 1:87-109.
[40] Tabibzadeh,S.S. Santhanam,U., Sehgal,P.B. et al 1989. Cytokine
induced production of IFN-β 2/IL-6 by freshly explanted human
endometrial stromal cells. Modulation by estradiol 17β. J. Immunol.,
142: 3134-3139.
[41] Wu, S.J., Liu, P.L,.Ng et al L.T., 2008. Tocotrienol-rich fraction of
palm oil exhibits anti-inflammatory property by suppressing the
expression of inflammatory mediators in human monocytic cells" Mol.
Nutr. Food Res 52: 921-929.
[42] B.C. Pearce, R.A. Parker, M.E. Deason, et al " Hypercholesterolaemic
activity of synthetic and natural tocotrienol. J. Med Chem., 35: 3595-
3606, 1992.
[43] Salari,P., Larijiani,B. Abdollahi,M. et al 2008. Association of
hyperhomocysteinemia with osteoporosis: A systematic review.
Therapy, 5: 215-222.
[44] Sharif ,P.S., Asalforoush, M. Ameri, F.et al 2010. The effect of n-3 fatty
acids on bone biomarkers in Iranian postmenopausal osteoporotic
women: A randomized clinical trial. Age, 32: 179-186.
[45] Sharif, P.S. Nikfar, S. Abdollahi, M.et al. 2011. Prevention of bone
resorption by intake of phytoestrogens in postmenopausal women: A
meta- analysis. Volume 33, number 3, 421-431.
[46] Sun,D., Krishnan, A., Zaman,K., et al 2003. Dietary n-3 fatty acids
decrease osteoclastogenesis and loss of bone mass in ovariectomized
mice. J. Bone Miner. Res., 18: 1206-1216.
[1] Michaëlsson,K., Melhus,H., Ferm,H., 2005. Genetic liability to
fractures in the elderly Arch. Intern. Med. 165:1825-1830.
[2] Slemenda, C.W., Christian,J.C., Williams,C.J. et al., 1991. Genetic
determinants of bone mass in adult women: a reevaluation of the twin
model and the potential importance of gene interaction on heritability
estimates" J. Bone Miner. Res. 6:561-567.
[3] Pooneh, S. and Mohammad, A. 2011. A comprehensive review of the
shared roles of inflammatory cytokines in osteoporosis and
cardiovascular disease as two common old people problem; actions
towards development of new drugs" International Journal of
Pharmacology 7(5): 552-567.
[4] Kong,Y.Y., Feige,U., Sarosi, Iet al., 1999. Activated T cells regulate
bone loss and joint destruction in adjuvant arthritis through
osteoprotegerin ligand" Nature 402:304-309.
[5] Manolagas, S.C., 2000. Birth and death of bone cells: Basic regulatory
mechanism and implications for the pathogenesis and treatment of
osteoporosis" Endocrinol.Rev., 21: 115-137.
[6] Goa,Y., Grassi, F, Robbie,M, Terauchi,M et al., 2007. IFN-╬│ stimulates
osteoclast formation and bone loss in vivo via antigen-driven T cell
activation" J.Clin Invest., 117:122-132.
[7] Miyaura,C., Kusano,K., Masuzawa,T., et al., 1995. Endogenous boneresorbing
factors in estrogen deficiency: Cooperative effects of IL-1 and
IL-6 J.Bone. Miner.Res., 10: 1365-1373.
[8] De Martins, M., Di Benedetto,M.C., Mengoli L.P., et al., 2006. Senile
osteoporosis: Is it an immune-mediated disease" Inflamm. Res., 55: 399-
404.
[9] Lacativa,P.G. and Farias, M.L, 2010. Osteoporosis and inflammatory
Arq. Bras. Endocrinol Metab., 54:123-132.
[10] Roggia,C. Gao,Y., Cenci, S., Weitzmann, M.N et al 2001. Upregulation
of TNF producing T cells in the bone marrow: A key
mechanism by which estrogen deficiency induces bone loss in vivo.
Proc. Natl.Acad.Sci. USA, 98: 13960-13965.
[11] Cenci,S. Toraldo,G., Weitzmann,M.N., Roggia C. et al., 2003.
Estrogen deficiency induces bone loss by increasing T cell proliferation
and life span through IFN-gamma-induced class II transactivator"
Proc.Natl.Acad. Sci USA., 100: 10405-10410.
[12] Serbinova,E.A. 1991. Alpha Tocotrienol Is A More Powerful membrane
Antioxidant Than Alpha Tocopherol", Oxid Damage Repair;77-81.
[13] Norazlina,M., Ling,H.L.R., Ima-Nirwana , S. et al., 2002. The effect of
vitamin E or calcium supplementation on bone mineral composition in
vitamin E deficient rats" Malaysia J. Biochem. Biol., 7: 1-5.
[14] Norazlina, M., Ima-Nirwana, S., Abd Gapor, M.T et al., 2002.
Tocotrienols are needed for normal bone calcification in growing female
rats. Asia Pacific J. Clin. Nutr., 11: 194-199.
[15] Norazlina, M., Ima-Nirwana, S., Gapor ,M.T., et al. 2000. Palm vitamin
E is comparable to alpha - tocopherol in maintaining bone mineral
density in ovariectomised female rats, Exp. Clin. Endocrinol. Diab.,
108: 305-310.
[16] Ima-Nirwana,S., Kiftiah, A., Sariza,T., Gapor,M.T., et al., 1999. Palm
vitamin E improves bone metabolism and survival rate in thyrotoxic rats.
Gen. Pharm., 32: 621-626.
[17] Nazrun, A.S., Norazlina,M., Norliza ,M., et al.2011. Tocotrienols as an
Anti-Osteoporotic Agent: The Progress So Far." International Journal of
Osteoporosis and Metabolic Disorders, 4: 1-14.
[18] Asmadi, A.Y.,Adam,A., Wan Ngah,W.Z., et al 2005. Tocotrienols and
╬▒- Tocopherol reduced acute and chronic lung lipid peroxidation
induced by paraquat in rats. Pak. J. Nutr., 4: 97-100.
[19] Nur Azlina,M.F., Nafeeza,M.I., Khalid , B.A.K. et al 2005. Effect of
tocotrienol on lipid peroxidation in experimental gastritis induced by
restraint stress. Pak. J. Nutr 4: 69-72 .
[20] Fan, Y. Liu, J., Wang,S. et al 2005.Functional proteome of bones in
rats with osteoporosis following ovariectomy. Life Sciences 76 :2893-
2901.
[21] Shen, S.H. Jing, Y.X. . Kuang , T.Y et al., 2003. Proteomics approach
to identify wound-response related proteins from rice leaf sheath.
Proteomics 3, 527-535.
[22] Mosekilde, L.and Mosekilde,L., et a 1990. Sex-difference in age-related
changes in vertebral body size, density and biomechanical competence
in normal individuals. Bone 11: 67-73.
[23] Kalu, D.N. 1991. The ovariectomised rat model of postmenopausal bone
loss. Bone Miner., 15: 175-191.
[24] Ima-Nirwana S., Norazlina, M.. Khali B.A.K d, et al 1998. Pattern of
bone mineral density in growing male and female rats gonadectomy. J.
Asean. Fed. Endoc. Soc 16: 21-26.
[25] Sack, M.N. Rader , D.J. Cannon R.O, et al 1994. Oestrogen and
inhibition of oxidation of low-density lipoproteins in postmenopausal
women" Lancet 343:269-270.
[26] Basu, S., Michaelsson,K., Olofsson,H., et al 2001. Association
between oxidative stress and bone mineral density" Biochem. Biophys.
Res. Commun., 288: 275-279.
[27] Badeau,M. Adlercreutz,H., Kaihovara,P., et al 2005. Estrogen A-ring
structure and antioxidant effect on lipoproteins. J. Steroid Biochem.
Mol. Biol,. 96: 271-278.
[28] Maggio,D., Barabani,M., Pierandrei,M., Polidori, M.C., et al 2003.
Marked decrease in plasma antioxidant in aged osteoporotic women:
Results of a cross-sectional study. J. Clin Endo, Metab., 88: 1523-1527
2003.
[29] Lean, J.M., Jagger, C.J. Kirsten, B. Fuller K., et al 2005. Hydrogen
peroxide is essential for estrogen-deficiency bone loss and osteoclast
formation. Endocrinol, 146: 728-735.
[30] Ahmad, N.S. Khalid, B.A.K., Luke, D.A. , et al. 2005. Tocotrienol
offers better protection than tocopherol from free radical-induced
damage of rat bone" Clin. Exp. Pharm. Physiol., 32: 761-770.
[31] Norazlina, M., Lukman, H.I, Nazrun A.S. , et al., 2007. Effects of
vitamin E supplementation on bone metabolism in nicotine-treated rats
Singapore Med. J. 48: 195-199.
[32] Hammer C.T and Wills E.D 1978. The role of lipid components of the
diet in the regulation of the fatty acid composition of the rat liver
endoplasmic reticulum and lipid peroxidation" Biochem. J., 174: 585-
595.
[33] Maniam, S. N. Mohamed,N. Shuid , A.N. et al., 2008. Palm tocotrienol
exerted better antioxidant activities in bone than alpha-tocopherol. Basic
Clin . Pharmacol.Toxicol., 103: 55-60.
[34] Wilkins, M. R., Pasquali, C., Appel, R. D., et al ".1996. From proteins to
proteomes: large scale protein identification by two-dimensional
electrophoresis and amino acid analysis." Biotechnology 14, 61-65.
[35] Kim, S. H. Jun, S. Hee-Sun, J. Sung-Kil, Let al 2005. Identification of
parathyroid hormone-regulated proteins in mouse bone marrow cells by
proteomics" Biochemical and Biophysical Research Communications
330 423-429.
[36] Chapam,C.M, Beilby, J.P., Humphries,S.E., et al 2003. Association of
an allelic variant of interleukin-6 with subclinical carotid atherosclerosis
in an Australian Community population" Eur. Heart. J., 24: 1494-1499,
2003.
[37] Manolagas S.G.and Jilka R.L. 1995. Mechanisms of disease: Bone
marrow, cytokines and bone remodeling- emerging insights into the
pathophysiology of osteoporosis" N. Engl. J. Med, 332:305-311.
[38] Scheidt-Nave,C. Bismar,H., Leidig-Bruckner,G. et al 2001. Serum
interleukin 6 is a major predictor of bone loss in women specific to the
first decade past menopause. J. Clin. Endocrinol Metab., 86: 2032-2042.
[39] Berton, B.E. 1996. The biological effects of interleukin 6" Med.Res.
Rev., 1:87-109.
[40] Tabibzadeh,S.S. Santhanam,U., Sehgal,P.B. et al 1989. Cytokine
induced production of IFN-β 2/IL-6 by freshly explanted human
endometrial stromal cells. Modulation by estradiol 17β. J. Immunol.,
142: 3134-3139.
[41] Wu, S.J., Liu, P.L,.Ng et al L.T., 2008. Tocotrienol-rich fraction of
palm oil exhibits anti-inflammatory property by suppressing the
expression of inflammatory mediators in human monocytic cells" Mol.
Nutr. Food Res 52: 921-929.
[42] B.C. Pearce, R.A. Parker, M.E. Deason, et al " Hypercholesterolaemic
activity of synthetic and natural tocotrienol. J. Med Chem., 35: 3595-
3606, 1992.
[43] Salari,P., Larijiani,B. Abdollahi,M. et al 2008. Association of
hyperhomocysteinemia with osteoporosis: A systematic review.
Therapy, 5: 215-222.
[44] Sharif ,P.S., Asalforoush, M. Ameri, F.et al 2010. The effect of n-3 fatty
acids on bone biomarkers in Iranian postmenopausal osteoporotic
women: A randomized clinical trial. Age, 32: 179-186.
[45] Sharif, P.S. Nikfar, S. Abdollahi, M.et al. 2011. Prevention of bone
resorption by intake of phytoestrogens in postmenopausal women: A
meta- analysis. Volume 33, number 3, 421-431.
[46] Sun,D., Krishnan, A., Zaman,K., et al 2003. Dietary n-3 fatty acids
decrease osteoclastogenesis and loss of bone mass in ovariectomized
mice. J. Bone Miner. Res., 18: 1206-1216.
@article{"International Journal of Medical, Medicine and Health Sciences:59533", author = "Patrick Nwabueze Okechukwu and Ima Nirwana Soelaiman and Gabriele Anisah Ruth Froemming and Mohd Yusri Idorus and Norazlina Mohamed", title = "Bone Proteome Study in Ovariectomised Rats Supplemented with Palm Vitamin E", abstract = "Supplementation of palm vitamin E has been reported
to prevent loss of bone density in ovariectomised female rats. The
mechanism by which palm vitamin E exerts these effects is still
unknown. We hypothesized that palm vitamin E may act by
preventing the protein expression changes. Two dimensional poly
acyrilamide gel electrophoresis (2-D PAGE) and PD Quest software
genomic solutions Investigator (proteomics) was used to analyze the
differential protein expression profile in femoral and humeri bones
harvested from three groups of rats; sham-operated rats (SO),
ovariectomised rats (Ovx) and ovariectomised rats supplemented for
2 months with palm vitamin E. The results showed that there were
over 300 valued spot on each of the groups PVE and OVX as
compared to about 200 in SO. Comparison between the differential
protein expression between OVX and PVE groups showed that ten
spots were down –regulated in OVX but up-regulated in PVE. The
ten differential spots were separately named P1-P10. The
identification and understanding of the pathway of the differential
protein expression among the groups is ongoing and may account for
the molecular mechanism through which palm vitamin E exert its
anti-osteoporotic effect.", keywords = "Palm vitamin E, ovariectomised, osteoporosis protein expression, 2-d-page.", volume = "6", number = "12", pages = "697-5", }
