Effects of (22s,23s)- and (22r,23r)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-ones on cholesteryl esters biosynthesis and acyl-CoA:cholesterol acyl transferase activity in Hep G2 cells
Novel synthetic oxysterols (22S,23S)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-one (I) and (22R,23R)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-one (II) influenced cholesteryl esters biosynthesis in human hepatoma Hep G2 cell line from [14C]acetate (85% and 180% compared to control at the concentrations of 5 μМ). The level of cholesteryl esters biosynthesis in Hep G2 cells from [14C]oleate increased in the presence of ketosterol (I) in a dose dependent manner, whereas the level of cholesteryl esters biosynthesis in the presence of ketosterol (II) reached the maximal value (269±20% from control) at the concentration of 1 µM. In a cell free system ketosterol (I) increased the rate of ACAТ-dependent cholesterol acylation like 25-hydroxycholesterol, however, ketosterol (II), efficiently stimulating initial rate of АСАТ-catalyzed cholesterol esterification, caused in rapid inactivation of this enzyme.
Download PDF:
Keywords: oxysterols, cholesterol, cholesteryl esters, ACAT, Hep G2 cells
Citation:
Mehtiev A.R., Kozlova N.I., Skripnik V.V., Misharin A.Yu. (2008) Effects of (22s,23s)- and (22r,23r)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-ones on cholesteryl esters biosynthesis and acyl-CoA:cholesterol acyl transferase activity in Hep G2 cells. Biomeditsinskaya Khimiya, 54(3), 341-348.
Mehtiev A.R. et al. Effects of (22s,23s)- and (22r,23r)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-ones on cholesteryl esters biosynthesis and acyl-CoA:cholesterol acyl transferase activity in Hep G2 cells // Biomeditsinskaya Khimiya. - 2008. - V. 54. -N 3. - P. 341-348.
Mehtiev A.R. et al., "Effects of (22s,23s)- and (22r,23r)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-ones on cholesteryl esters biosynthesis and acyl-CoA:cholesterol acyl transferase activity in Hep G2 cells." Biomeditsinskaya Khimiya 54.3 (2008): 341-348.
Mehtiev, A. R., Kozlova, N. I., Skripnik, V. V., Misharin, A. Yu. (2008). Effects of (22s,23s)- and (22r,23r)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-ones on cholesteryl esters biosynthesis and acyl-CoA:cholesterol acyl transferase activity in Hep G2 cells. Biomeditsinskaya Khimiya, 54(3), 341-348.
Мехтиев А.Р., Морозевич Г.Е., Иванов В.С., Мишарин А.Ю. (2007) Биомед. xимия, 53, 321-327. Scholar google search
Oelkers P. Behari A., Cromley D., Billheimer J.T., Sturley S.L. (1998) J. Biol. Chem., 273, 26765-26771. Scholar google search
Buhman K.F., Accad M., Farese R.V. (2000) Biochim. Biophys. Acta, 1529, 142-154. Scholar google search
Chang T.Y., Сhang C.C.Y., Lu X., Lin S. (2001) J. Lipid Res., 42, 1933-1938. Scholar google search
Smith J.L., Rangaraj K., Simpson R., Maclean D.J., Nathanson L.K., Stuart K.A., Scott S.P., Ramm G.A., de Jersey J. (2004). J. Lipid Res., 45, 686-696. Scholar google search
Spady D.K., Willard M.N., Meidell R.S. (2000) J. Biol. Chem., 275, 27005-27012. Scholar google search
Rudel L.R., Lee R.G., Parini P. (2005) Arterioscler. Thromb. Vasc. Biol., 25, 1112-1118. Scholar google search
Smith P.K., Krohn R.I., Hermanson G.T., Mallia A.K., Gartner F.H., Provenzano M.D., Fujimoto E.K., Goeke N.M., Olson B.J., Klenk D.C. (1985) Anal. Biochem., 150, 76-85. Scholar google search
Goldstein J.L., Anderson R.G.W., Brown M.S. (1979) Methods Enzymol., 98, 241-261. Scholar google search
Cheng D., Chang C.C.Y., Qu X.-M., Chang T.Y. (1995) J. Biol. Chem., 270, 685-695. Scholar google search
Miller S.C., Melnikovich G. (1984). J. Lipid Res., 25, 991-999. Scholar google search
Chang C.C.Y., Chen J., Thomas M.A., Cheng D. Del Priore V.A., Newton R.S., Pape M.E., Chang T.Y. (1995) J. Biol. Chem. 270, 29532-29540. Scholar google search
Chang C.C.Y., Lee C.Y.G., Chang E.T., Cruz J.C., Levesque M.C., Chang T.Y. (1998) J. Biol. Chem. 273, 35132-35141. Scholar google search
Zhang Y., Yu C., Liu J., Spencer T.A., Chang C.C.Y., Chang T.Y. (2003) J. Biol. Chem., 278, 11642-11647. Scholar google search
