Production of 22-hydroxy metabolites of vitamin D 3 by cytochrome P450scc (CYP11A1) and analysis of their biological activities on skin cells

Drug Metabolism and Disposition

Volumn 39, Issue 9, 2011, Pages 1577-1588

  Tuckey, Robert C ^a   Li, Wei ^b   Shehabi, Haleem Z ^c   Janjetovic, Zorica ^b   Nguyen, Minh N ^a   Kim, Tae Kang ^b   Chen, Jianjun ^b   Howell, Danielle E ^b   Benson, Heather A E ^c   Sweatman, Trevor ^b   Baldisseri, Donna M ^d   Slominski, Andrzej ^b  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^c CURTIN UNIVERSITY   (Australia)

^d BRUKER BIOSPIN CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

20 HYDROXYVITAMIN D3; 20,22 DIHYDROXYVITAMIN D3; 20,23 DIHYDROXYVITAMIN D3; 22 HYDROXYVITAMIN D3; CALCITRIOL; CHOLESTEROL MONOOXYGENASE (SIDE CHAIN CLEAVING); COLECALCIFEROL; COLECALCIFEROL DERIVATIVE; DRUG METABOLITE; INVOLUCRIN; MESSENGER RNA; TRIHYDROXYCOLECALCIFEROL; UNCLASSIFIED DRUG; VITAMIN D RECEPTOR;

ARTICLE; CELL DIFFERENTIATION; CELL NUCLEUS; CELL PROLIFERATION; CHEMICAL REACTION; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOPLASM; DRUG ACTIVITY; DRUG EFFECT; DRUG IDENTIFICATION; DRUG METABOLISM; DRUG STRUCTURE; ENZYME ACTIVITY; GENE ACTIVATION; GENE EXPRESSION; GENETIC HETEROGENEITY; HUMAN; HUMAN CELL; INTRACELLULAR TRANSPORT; KERATINOCYTE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TRANSPORT;

25-HYDROXYVITAMIN D3 1-ALPHA-HYDROXYLASE; CALCIFEDIOL; CELL PROLIFERATION; CELLS, CULTURED; CHOLECALCIFEROL; CHOLESTEROL SIDE-CHAIN CLEAVAGE ENZYME; DIHYDROXYCHOLECALCIFEROLS; HUMANS; HYDROXYCHOLECALCIFEROLS; KERATINOCYTES; MAGNETIC RESONANCE SPECTROSCOPY; PROTEIN PRECURSORS; PROTEIN TRANSPORT; RECEPTORS, CALCITRIOL; SKIN; STEROID HYDROXYLASES;

EID: 80051975233     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.111.040071     Document Type: Article

References (34)

1. Burstein S., Middleditch BS, and Gut M. (1975) Mass spectrometric study of the enzymatic conversion of cholesterol to (22R)-22-hydroxycholesterol, (20R,22R)-20,22-dihydroxycholesterol, and pregnenolone, and of (22R)-22-hydroxycholesterol to the glycol and pregnenolone in bovine adrenocortical preparations. Mode of oxygen incorporation. J Biol Chem 250:9028-9037.
2. De Caprio J., Yun J, and Javitt N.B. (1992) Bile acid and sterol solubilization in 2- Hydroxypropyl- Hydroxypropylβ- Hydroxypropylβ Cyclodextrin. J Lipid Res 33:441-443.
3. 3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1). Proc Natl Acad Sci USA 100:14754-14759.
4. Headlam M.J., Wilce MC, and Tuckey R.C. (2003) The F- G loop region of cytochrome P450scc (CYP11A1) interacts with the phospholipid membrane. BBA Biomembranes 1617:96-108. (Pubitemid 37456717)
5. 3-1α-hydroxylase) of bovine kidney mitochondria. Biochem Biophys Res Commun 105:320-327.
6. Janjetovic Z., Tuckey R.C., Nguyen M.N., Thorpe E.M. Jr, and Slominski A.T. (2010) 20,23- Dihydroxyvitamin D3, novel P450scc product, stimulates differentiation and inhibits proliferation and NF- Dihydroxyvitamin D3, novel P450scc product, stimulates differentiation and inhibits proliferation and NFκB activity in human keratinocytes. J Cell Physiol 223:36-48.
7. Janjetovic Z., Zmijewski M.A., Tuckey R.C., DeLeon D.A., Nguyen M.N., Pfeffer LM, and Slominski A.T. (2009) 20- Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF- Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NFκB activity by increasing IκBα levels in human keratinocytes. PLoS ONE 4:e5988.
8. Lambeth J.D., Kitchen S.E., Farooqui A.A., Tuckey R, and Kamin H. (1982) Cytochrome P-450scc- 450sccSubstrate interactions. Studies of binding and catalytic activity using hydroxycholesterols. J Biol Chem 257:1876-1884.
9. Li W., Chen J., Janjetovic Z., Kim T.K., Sweatman T., Lu Y., Zjawiony J., Tuckey R.C., Miller D, and Slominski A. (2010) Chemical synthesis of 20S- Hydroxyvitamin D3, which shows antiproliferative activity. Steroids 75:926-935.
10. Mast N., Annalora A.J., Lodowski D.T., Palczewski K., Stout CD, and Pikuleva I.A. (2011) Structural basis for three- Step sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1. J Biol Chem 286:5607-5613.
11. Nguyen M.N., Slominski A., Li W., Ng YR, and Tuckey R.C. (2009) Metabolism of vitamin D2 to 17,20,24- Trihydroxyvitamin D2 by cytochrome P450scc (CYP11A1). Drug Metab Dispos 37:761-767.
12. Omura T and Sato R. (1964) The carbon monoxide- Binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239:2370-2378.
13. Prosser DE and Jones G. (2004) Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci 29:664-673. (Pubitemid 39491265)
14. Schuster I. (2011) Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta 1814:186-199.
15. 2 and 17,20-dihydroxyvitamin D2. FEBS J 273:2891-2901.
16. Slominski A., Semak I., Zjawiony J., Wortsman J., Gandy M.N., Li J., Zbytek B., Li W, and Tuckey R.C. (2005a) Enzymatic metabolism of ergosterol by cytochrome P450scc to biologically active 17α,24- Dihydroxyergosterol. Chem Biol 12:931-939. (Pubitemid 41206807)
17. Slominski A., Semak I., Zjawiony J., Wortsman J., Li W., Szczesniewski A, and Tuckey R.C. (2005b) The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism. FEBS J 272:4080-4090. (Pubitemid 41160916)
18. Slominski A., Zjawiony J., Wortsman J., Semak I., Stewart J., Pisarchik A., Sweatman T., Marcos J., Dunbar C, and Tuckey R.C. (2004) A novel pathway for sequential transformation of 7- Dehydrocholesterol and expression of the P450scc system in mammalian skin. Eur J Biochem 271:4178-4188. (Pubitemid 39506746)
19. Slominski A.T., Janjetovic Z., Fuller B.E., Zmijewski M.A., Tuckey R.C., Nguyen M.N., Sweatman T., Li W., Zjawiony J., Miller D., et al. (2010) Products of vitamin D3 or 7- Dehydrocholesterol metabolism by cytochrome P450scc show anti- Dehydrocholesterol metabolism by cytochrome P450scc show antiLeukemia effects, having low or absent calcemic activity. PLoS ONE 5:e9907.
20. 2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells. Am J Physiol Cell Physiol 300:C526-C541.
21. Slominski A.T., Zmijewski M.A., Semak I., Sweatman T., Janjetovic Z., Li W., Zjawiony JK, and Tuckey R.C. (2009) Sequential metabolism of 7- Dehydrocholesterol to steroidal 5,7- Dehydrocholesterol to steroidal 5,7Dienes in adrenal glands and its biological implication in the skin. PLoS ONE 4:e4309.
22. Strushkevich N., Mackenzie F., Cherkesova T., Grabovec I., Usanov S, and Park H.W. (2011) Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc Natl Acad Sci USA 108:10139-10143.
23. 3, which has altered biological activity. Drug Metab Dispos 38:1553-1559.
24. 3 1α-hydroxylase (CYP27B1). J Steroid Biochem Mol Biol 119:171-179.
25. Tuckey R.C. (2005) Progesterone synthesis by the human placenta. Placenta 26:273-281.
26. scc. Biochim Biophys Acta 1163:185-194.
27. Tuckey RC and Cameron K.J. (1993b) Side- Chain specificities of human and bovine cytochromes P-450scc. Eur J Biochem 217:209-215. (Pubitemid 23305288)
28. sccinto phosphatidylcholine vesicles. J Biol Chem 257:2887-2893.
29. 3 by cytochrome P450scc (CYP11A1). FEBS J 275:2585-2596.
30. 3 metabolism by cytochrome P450scc (CYP11A1) in phospholipid vesicles and cyclodextrin. Int J Biochem Cell Biol 40:2619-2626.
31. Tuckey RC and Sadleir J. (1999) The concentration of adrenodoxin reductase limits cytochrome P450scc activity in the human placenta. Eur J Biochem 263:319-325. (Pubitemid 29337021)
32. scc incorporated into artificial phospholipid vesicles. Int J Biochem 16:497-503.
33. Woods S.T., Sadleir J., Downs T., Triantopoulos T., Headlam MJ, and Tuckey R.C. (1998) Expression of catalytically active human cytochrome P450scc in Escherichia coli and mutagenesis of isoleucine- 462. Arch Biochem Biophys 353:109-115. (Pubitemid 28373035)
34. 3 hydroxylation by cytochrome P450scc, stimulates keratinocytes differentiation. J Invest Dermatol 128:2271-2280.