Novel vitamin D photoproducts and their precursors in the skin

Dermato-Endocrinology

Volumn 5, Issue 1, 2013, Pages 7-19

  Slominski, Andrzej T ^a   Kim, Tae Kang ^a   Zmijewski, Michal A ^b   Janjetovic, Zorica ^a   Li, Wei ^a   Chen, Jianjun ^a   Kusniatsova, Ekaterina I ^c   Semak, Igor ^c   Postlethwaite, Arnold ^a   Miller, Duane D ^a   Zjawiony, Jordan K ^d   Tuckey, Robert C ^e  

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

^b MEDICAL UNIVERSITY OF GDANSK   (Poland)

^c BELARUSIAN STATE UNIVERSITY   (Belarus)

^d UNIVERSITY OF MISSISSIPPI   (United States)

^e UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

Author keywords

5,7 dienes; Dermal fibroblasts; Keratinocytes; Melanocytes; Melanoma cells; Skin; Vitamin D

Indexed keywords

7 DEHYDROCHOLESTEROL; CHOLESTEROL MONOOXYGENASE (SIDE CHAIN CLEAVING); ESTROGEN; SECOSTEROID; STEROID; VITAMIN D; VITAMIN D RECEPTOR;

BIOLOGICAL ACTIVITY; CELL ORGANELLE; CELL PROLIFERATION; CHOLESTEROL METABOLISM; ENZYME METABOLISM; ESTROGEN SYNTHESIS; HUMAN; KERATINOCYTE; LEUKEMIA; MELANOCYTE; NONHUMAN; PRECURSOR; REVIEW; SKIN; SKIN FIBROBLAST; SMITH LEMLI OPITZ SYNDROME; STEROIDOGENESIS; ULTRAVIOLET B RADIATION;

EID: 84876751387     PISSN: 19381972     EISSN: 19381980     Source Type: Journal    
DOI: 10.4161/derm.23938     Document Type: Review

References (82)

1. Slominski A, Wortsman J, Paus R, Elias PM, Tobin DJ, Feingold KR. Skin as an endocrine organ: implications for its function. Drug Discov Today Dis Mech 2008; 5: 137-44; PMID:19492070; http://dx.doi.org/10.1016/j.ddmec.2008.04.004.
2. Slominski A, Wortsman J. Neuroendocrinology of the skin. Endocr Rev 2000; 21: 457-87; PMID:11041445; http://dx.doi.org/10.1210/er.21.5.457.
3. Slominski A, Wortsman J, Luger T, Paus R, Solomon S. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Physiol Rev 2000; 80: 979-1020; PMID:10893429.
4. Slominski A, Zjawiony J, Wortsman J, Semak I, Stewart J, Pisarchik A, et al. A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin. Eur J Biochem 2004; 271: 4178-88; PMID:15511223; http://dx.doi.org/10.1111/j.1432-1033.2004.04356.x.
5. Slominski AT, Zmijewski MA, Semak I, Sweatman T, Janjetovic Z, Li W, et al. Sequential metabolism of 7-dehydrocholesterol to steroidal 5,7-dienes in adrenal glands and its biological implication in the skin. PLoS One 2009; 4: e4309; PMID:19190754; http://dx.doi.org/10.1371/journal.pone.0004309.
6. Slominski AT, Kim TK, Chen J, Nguyen MN, Li W, Yates CR, et al. Cytochrome P450scc-dependent metabolism of 7-dehydrocholesterol in placenta and epidermal keratinocytes. Int J Biochem Cell Biol 2012; 44: 2003-18; PMID:22877869; http://dx.doi.org/10.1016/j.biocel.2012.07.027.
7. Tuckey RC, Nguyen MN, Chen J, Slominski AT, Baldisseri DM, Tieu EW, et al. Human cytochrome P450scc (CYP11A1) catalyzes epoxide formation with ergosterol. Drug Metab Dispos 2012; 40: 436-44; PMID:22106170; http://dx.doi.org/10.1124/dmd.111.042515.
8. Slominski A, Semak I, Zjawiony J, Wortsman J, Gandy MN, Li J, et al. Enzymatic metabolism of ergosterol by cytochrome p450scc to biologically active 17alpha,24- dihydroxyergosterol. Chem Biol 2005; 12: 931-9; PMID:16125105; http://dx.doi.org/10.1016/j.chembiol. 2005.06.010.
9. Slominski A, Semak I, Zjawiony J, Wortsman J, Li W, Szczesniewski A, et al. The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism. FEBS J 2005; 272: 4080-90; PMID:16098191; http://dx.doi.org/10.1111/ j.1742-4658.2005.04819.x.
10. Tuckey RC, Janjetovic Z, Li W, Nguyen MN, Zmijewski MA, Zjawiony J, et al. Metabolism of 1alpha-hydroxyvitamin D3 by cytochrome P450scc to biologically active 1alpha,20-dihydroxyvitamin D3. J Steroid Biochem Mol Biol 2008; 112: 213-9; PMID:19000766; http://dx.doi.org/10.1016/j.jsbmb.2008.10.005.
11. Tuckey RC, Li W, Zjawiony JK, Zmijewski MA, Nguyen MN, Sweatman T, et al. Pathways and products for the metabolism of vitamin D3 by cytochrome P450scc. FEBS J 2008; 275: 2585-96; PMID:18410379; http://dx.doi.org/10.1111/j.1742-4658. 2008.06406.x.
12. Tuckey RC, Li W, Shehabi HZ, Janjetovic Z, Nguyen MN, Kim TK, et al. Production of 22-hydroxy metabolites of vitamin d3 by cytochrome p450scc (CYP11A1) and analysis of their biological activities on skin cells. Drug Metab Dispos 2011; 39: 1577-88; PMID:21677063; http://dx.doi.org/10.1124/dmd.111. 040071.
13. Slominski AT, Kim TK, Shehabi HZ, Semak I, Tang EKY, Nguyen MN, et al. In vivo evidence for a novel pathway of vitamin D, metabolism initiated by P450scc and modified by CYP27B1. FASEB J 2012; 26: 3901-15; PMID:22683847; http://dx.doi.org/10.1096/fj.12-208975.
14. Tieu EW, Li W, Chen J, Baldisseri DM, Slominski AT, Tuckey RC. Metabolism of cholesterol, vitamin D3 and 20-hydroxyvitamin D3 incorporated into phospholipid vesicles by human CYP27A1. J Steroid Biochem Mol Biol 2012; 129: 163-71; PMID:22210453; http://dx.doi.org/10.1016/j.jsbmb.2011.11.012.
15. Tang EK, Li W, Janjetovic Z, Nguyen MN, Wang Z, Slominski A, et al. Purified mouse CYP27B1 can hydroxylate 20,23-dihydroxyvitamin D3, producing 1alpha,20,23-trihydroxyvitamin D3, which has altered biological activity. Drug Metab Dispos 2010; 38: 1553-9; PMID:20554701; http://dx.doi.org/10.1124/dmd.110. 034389.
16. Tang EK, Voo KJ, Nguyen MN, Tuckey RC. Metabolism of substrates incorporated into phospholipid vesicles by mouse 25-hydroxyvitamin D3 1alpha-hydroxylase (CYP27B1). J Steroid Biochem Mol Biol 2010; 119: 171-9; PMID:20193763; http://dx.doi.org/10.1016/j.jsbmb.2010.02.022.
17. Slominski A, Semak I, Wortsman J, Zjawiony J, Li W, Zbytek B, et al. An alternative pathway of vitamin D metabolism. Cytochrome P450scc (CYP11A1)- mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2. FEBS J 2006; 273: 2891-901; PMID:16817851; http://dx.doi.org/10.1111/j.1742-4658. 2006.05302.x.
18. Nguyen MN, Slominski A, Li W, Ng YR, Tuckey RC. Metabolism of vitamin d2 to 17,20,24-trihydroxyvitamin d2 by cytochrome p450scc (CYP11A1). Drug Metab Dispos 2009; 37: 761-7; PMID:19116262; http://dx.doi.org/10.1124/dmd.108.025619.
19. Tuckey RC. Progesterone synthesis by the human placenta. Placenta 2005; 26: 273-81; PMID:15823613; http://dx.doi.org/10.1016/j.placenta.2004.06.012.
20. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 2011; 32: 81-151; PMID:21051590; http://dx.doi.org/10.1210/er.2010-0013.
21. Tieu EW, Tang EK, Chen J, Li W, Nguyen MN, Janjetovic Z, et al. Rat CYP24A1 acts on 20-hydroxyvitamin D(3) producing hydroxylated products with increased biological activity. Biochem Pharmacol 2012; 84: 1696-704; PMID:23041230; http://dx.doi.org/10.1016/j.bcp.2012.09.032.
22. Slominski AT, Kim TK, Janjetovic Z, Tuckey RC, Bieniek R, Yue J, et al. 20-Hydroxyvitamin D2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells. Am J Physiol Cell Physiol 2011; 300: C526-41; PMID:21160030; http://dx.doi.org/10.1152/ajpcell.00203.2010.
23. Wang J, Slominski A, Tuckey RC, Janjetovic Z, Kulkarni A, Chen J, et al. 20-hydroxyvitamin D, inhibits proliferation of cancer cells with high efficacy while being non-toxic. Anticancer Res 2012; 32: 739-46; PMID:22399586.
24. Slominski AT, Janjetovic Z, Kim TK, Wright AC, Grese LN, Riney SJ, et al. Novel vitamin D hydroxyderivatives inhibit melanoma growth and show differential effects on normal melanocytes. Anticancer Res 2012; 32: 3733-42; PMID:22993313.
25. Slominski AT, Li W, Bhattacharya SK, Smith RA, Johnson PL, Chen J, et al. Vitamin D analogs 17,20S(OH)2pD and 17,20R(OH)2pD are noncalcemic and exhibit antifibrotic activity. J Invest Dermatol 2011; 131: 1167-9; PMID:21228816; http://dx.doi.org/10.1038/jid.2010.425.
26. Slominski AT, Janjetovic Z, Fuller BE, Zmijewski MA, Tuckey RC, Nguyen MN, et al. Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity. PLoS One 2010; 5: e9907; PMID:20360850; http://dx.doi.org/10.1371/ journal. pone.0009907.
27. Li W, Chen J, Janjetovic Z, Kim TK, Sweatman T, Lu Y, et al. Chemical synthesis of 20S-hydroxyvitamin D3, which shows antiproliferative activity. Steroids 2010; 75: 926-35; PMID:20542050; http://dx.doi.org/10.1016/j.steroids. 2010.05.021.
28. Janjetovic Z, Brozyna AA, Tuckey RC, Kim TK, Nguyen MN, Jozwicki W, et al. High basal NF-κB activity in nonpigmented melanoma cells is associated with an enhanced sensitivity to vitamin D3 derivatives. Br J Cancer 2011; 105: 1874-84; PMID:22095230; http://dx.doi.org/10.1038/bjc.2011.458.
29. Janjetovic Z, Tuckey RC, Nguyen MN, Thorpe EM Jr., Slominski AT. 20,23-dihydroxyvitamin D3, novel P450scc product, stimulates differentiation and inhibits proliferation and NF-kappaB activity in human keratinocytes. J Cell Physiol 2010; 223: 36-48; PMID:20020487.
30. Janjetovic Z, Zmijewski MA, Tuckey RC, DeLeon DA, Nguyen MN, Pfeffer LM, et al. 20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes. PLoS One 2009; 4: e5988; PMID:19543524; http://dx.doi.org/10.1371/journal.pone.0005988.
31. Zbytek B, Janjetovic Z, Tuckey RC, Zmijewski MA, Sweatman TW, Jones E, et al. 20-Hydroxyvitamin D3, a product of vitamin D3 hydroxylation by cytochrome P450scc, stimulates keratinocyte differentiation. J Invest Dermatol 2008; 128: 2271-80; PMID:18368131; http://dx.doi.org/10.1038/jid.2008.62.
32. Marcos J, Guo LW, Wilson WK, Porter FD, Shackleton C. The implications of 7-dehydrosterol-7-reductase deficiency (Smith-Lemli-Opitz syndrome) to neurosteroid production. Steroids 2004; 69: 51-60; PMID:14715377; http://dx.doi.org/10.1016/j.steroids. 2003.09.013.
33. Shackleton C, Roitman E, Guo LW, Wilson WK, Porter FD. Identification of 7(8) and 8(9) unsaturated adrenal steroid metabolites produced by patients with 7-dehydrosterol-delta7-reductase deficiency (Smith- Lemli-Opitz syndrome). J Steroid Biochem Mol Biol 2002; 82: 225-32; PMID:12477489; http://dx.doi.org/10. 1016/S0960-0760(02)00155-3.
34. Kim TK, Chen J, Li W, Zjawiony J, Miller D, Janjetovic Z, et al. A new steroidal 5,7-diene derivative, 3beta-hydroxyandrosta-5,7-diene-17beta- carboxylic acid, shows potent anti-proliferative activity. Steroids 2010; 75: 230-9; PMID:20025893; http://dx.doi.org/10.1016/j.steroids.2009.12.004.
35. Zmijewski MA, Li W, Zjawiony JK, Sweatman TW, Chen J, Miller DD, et al. Photo-conversion of two epimers (20R and 20S) of pregna-5,7-diene-3beta, 17alpha, 20-triol and their bioactivity in melanoma cells. Steroids 2009; 74: 218-28; PMID:19028513; http://dx.doi.org/10.1016/j.steroids.2008.10.017.
36. Zmijewski MA, Li W, Zjawiony JK, Sweatman TW, Chen J, Miller DD, et al. Synthesis and photoconversion of androsta- and pregna-5,7-dienes to vitamin D3-like derivatives. Photochem Photobiol Sci 2008; 7: 1570-6; PMID:19037511; http://dx.doi.org/10.1039/b809005j.
37. Zmijewski MA, Li W, Chen J, Kim TK, Zjawiony JK, Sweatman TW, et al. Synthesis and photochemical transformation of 3beta,21-dihydroxypregna-5,7-dien- 20-one to novel secosteroids that show anti-melanoma activity. Steroids 2010; PMID:21070794.
38. Zmijewski MA, Li W, Chen J, Kim TK, Zjawiony JK, Sweatman TW, et al. Synthesis and photochemical transformation of 3β,21-dihydroxypregna-5,7- dien- 20-one to novel secosteroids that show anti-melanoma activity. Steroids 2010; 76: 193-203; PMID:21070794; http://dx.doi.org/10.1016/j.steroids.2010.10. 009.
39. Guryev O, Carvalho RA, Usanov S, Gilep A, Estabrook RW. A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1). Proc Natl Acad Sci U S A 2003; 100: 14754-9; PMID:14657394; http://dx.doi.org/10.1073/pnas.2336107100.
40. Holick MF. Vitamin D: A millenium perspective. J Cell Biochem 2003; 88: 296-307; PMID:12520530; http://dx.doi.org/10.1002/jcb.10338.
41. Bikle DD. Vitamin D: an ancient hormone. Exp Dermatol 2011; 20: 7-13; PMID:21197695; http://dx.doi.org/10.1111/j.1600-0625.2010.01202.x.
42. Tait AD, Hodge LC, Allen WR. The biosynthesis of 3 beta-hydroxy-5,7- androstadien-17-one by the horse fetal gonad. FEBS Lett 1985; 182: 107-10; PMID:3972117; http://dx.doi.org/10.1016/0014-5793(85)81164-9.
43. Savard K. The estrogens of the pregnant mare. Endocrinology 1961; 68: 411-6; PMID:13746869; http://dx.doi.org/10.1210/endo-68-3-411.
44. Foster SJ, Marshall DE, Houghton E, Gower DB. Investigations into the biosynthetic pathways for classical and ring B-unsaturated oestrogens in equine placental preparations and allantochorionic tissues. J Steroid Biochem Mol Biol 2002; 82: 401-11; PMID:12589948; http://dx.doi.org/10.1016/S0960-0760(02)00224- 8.
45. Numazawa M, Osawa Y. Equilin and equilenin biosynthesis. Stereochemistry of aromatization of 3-hydroxy- 3,5,7-androstatrien-17-one by horse placenta. J Steroid Biochem 1987; 26: 137-43; PMID:3821102; http://dx.doi.org/10.1016/0022- 4731(87)90042-2.
46. Stárka L, Breuer H, Cedard L. Biosynthesis of equilin and related ring B unsaturated oestrogens in perfused human placenta. J Endocrinol 1966; 34: 447-56; PMID:5933098; http://dx.doi.org/10.1677/joe.0.0340447.
47. Raeside JI, Renaud RL. Identification of 3 betahydroxy- 5,7-androstadien-17-one as a secretory product of the fetal horse gonad in vivo and in vitro. J Endocrinol 1985; 107: 415-9; PMID:4067494; http://dx.doi.org/10. 1677/joe.0.1070415.
48. Shackleton CH. Role of a disordered steroid metabolome in the elucidation of sterol and steroid biosynthesis. Lipids 2012; 47: 1-12; PMID:21874273; http://dx.doi.org/10.1007/s11745-011-3605-6.
49. Shackleton CH, Roitman E, Kratz LE, Kelley RI. Equine type estrogens produced by a pregnant woman carrying a Smith-Lemli-Opitz syndrome fetus. J Clin Endocrinol Metab 1999; 84: 1157-9; PMID:10084612; http://dx.doi.org/10.1210/jc. 84.3.1157.
50. Slominski A, Wortsman J, Foecking MF, Shackleton CH, Gomez-Sanchez CE, Szczesniewski A. Gas chromatography/mass spectrometry characterization of corticosteroid metabolism in human immortalized keratinocytes. J Invest Dermatol 2002; 118: 310-5; PMID:11841549; http://dx.doi.org/10.1046/j.0022-202x.2001. 01648.x.
51. Shackleton CH, Roitman E, Kratz L, Kelley R. Dehydro-oestriol and dehydropregnanetriol are candidate analytes for prenatal diagnosis of Smith-Lemli- Opitz syndrome. Prenat Diagn 2001; 21: 207-12; PMID:11260610; http://dx.doi.org/10.1002/1097-0223(200103)21:33.0.CO;2-I.
52. Slominski AT, Zmijewski MA, Skobowiat C, Zbytek B, Slominski RM, Steketee JD. Sensing the environment: regulation of local and global homeostasis by the skin's neuroendocrine system. Adv Anat Embryol Cell Biol 2012; 212: v, vii, 1-115; PMID:22894052.
53. Slominski A, Tobin DJ, Shibahara S, Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev 2004; 84: 1155-228; PMID:15383650; http://dx.doi.org/10.1152/physrev. 00044.2003.
54. Slominski A, Zbytek B, Nikolakis G, Manna PR, Skobowiat C, Zmijewski M, et al. Steroidogenesis in the skin: implications for local immune functions. J Steroid Biochem Mol Biol 2013; In press.
55. Slominski A, Ermak G, Mihm M. ACTH receptor, CYP11A1, CYP17 and CYP21A2 genes are expressed in skin. J Clin Endocrinol Metab 1996; 81: 2746-9; PMID:8675607; http://dx.doi.org/10.1210/jc.81.7.2746.
56. Slominski A, Wortsman J, Tuckey RC, Paus R. Differential expression of HPA axis homolog in the skin. Mol Cell Endocrinol 2007; 265-266: 143-9; PMID:17197073; http://dx.doi.org/10.1016/j.mce.2006.12.012.
57. Lu Y, Chen J, Janjetovic Z, Michaels P, Tang EK, Wang J, et al. Design, synthesis, and biological action of 20R-hydroxyvitamin D3. J Med Chem 2012; 55: 3573-7; PMID:22404326; http://dx.doi.org/10.1021/jm201478e.
58. Hua Z, Carcache DA, Tian Y, Li YM, Danishefsky SJ. The synthesis and preliminary biological evaluation of a novel steroid with neurotrophic activity: NGA0187. J Org Chem 2005; 70: 9849-56; PMID:16292815; http://dx.doi.org/10. 1021/jo051556d.
59. Holick MF, Clark MB. The photobiogenesis and metabolism of vitamin D. Fed Proc 1978; 37: 2567-74; PMID:212325.
60. Holick MF, Tian XQ, Allen M. Evolutionary importance for the membrane enhancement of the production of vitamin D3 in the skin of poikilothermic animals. Proc Natl Acad Sci U S A 1995; 92: 3124-6; PMID:7724526; http://dx.doi.org/10.1073/pnas.92.8.3124.
61. Zmijewski MA, Li W, Zjawiony JK, Sweatman TW, Chen J, Miller DD, et al. Photo-conversion of two epimers (20R and 20S) of pregna-5,7-diene-3beta, 17alpha, 20-triol and their bioactivity in melanoma cells. Steroids 2009; 74: 218-28; PMID:19028513; http://dx.doi.org/10.1016/j.steroids.2008.10.017.
62. Slominski A, Li W, Zbytek B, Tuckey RC, Zjawiony J, Nguyen MN, et al. Enzymatic production or chemical synthesis and uses for 5,7-dienes and UVB conversion products thereof. US2011/0118228A1 2011.
63. Webb AR, DeCosta BR, Holick MF. Sunlight regulates the cutaneous production of vitamin D3 by causing its photodegradation. J Clin Endocrinol Metab 1989; 68: 882-7; PMID:2541158; http://dx.doi.org/10.1210/jcem-68-5-882.
64. Slominski AT, Zmijewski MA, Semak I, Sweatman T, Janjetovic Z, Li W, et al. Sequential metabolism of 7-dehydrocholesterol to steroidal 5,7-dienes in adrenal glands and its biological implication in the skin. PLoS One 2009; 4: e4309; PMID:19190754; http://dx.doi.org/10.1371/journal.pone.0004309.
65. Plum LA, Prahl JM, Ma X, Sicinski RR, Gowlugari S, Clagett-Dame M, et al. Biologically active noncalcemic analogs of 1alpha,25-dihydroxyvitamin D with an abbreviated side chain containing no hydroxyl. Proc Natl Acad Sci U S A 2004; 101: 6900-4; PMID:15118084; http://dx.doi.org/10.1073/pnas.0401656101.
66. Murari MP, Londowski JM, Bollman S, Kumar R. Synthesis and biological activity of 3 beta-hydroxy- 9,10-secopregna-5,7,10[19]-triene-20-one: a side chain analogue of vitamin D3. J Steroid Biochem 1982; 17: 615-9; PMID:6294414; http://dx.doi.org/10.1016/0022-4731(82)90562-3.
67. Holick MF, Garabedian M, Schnoes HK, DeLuca HF. Relationship of 25-hydroxyvitamin D3 side chain structure to biological activity. J Biol Chem 1975; 250: 226-30; PMID:1141205.
68. Szyszka P, Zmijewski MA, Slominski AT. New vitamin D analogs as potential therapeutics in melanoma. Expert Rev Anticancer Ther 2012; 12: 585-99; PMID:22594894; http://dx.doi.org/10.1586/era.12.40.
69. Zmijewski MA, Li W, Chen J, Kim TK, Zjawiony JK, Sweatman TW, et al. Synthesis and photochemical transformation of 3β,21-dihydroxypregna-5,7- dien- 20-one to novel secosteroids that show anti-melanoma activity. Steroids 2011; 76: 193-203; PMID:21070794; http://dx.doi.org/10.1016/j.steroids.2010.10. 009.
70. Kim TK, Wang J, Janjetovic Z, Chen J, Tuckey RC, Nguyen MN, et al. Correlation between secosteroidinduced vitamin D receptor activity in melanoma cells and computer-modeled receptor binding strength. Mol Cell Endocrinol 2012; 361: 143-52; PMID:22546549; http://dx.doi.org/10.1016/j.mce.2012.04.001.
71. Slominski A, Janjetovic Z, Tuckey RC, Nguyen MN, Bhattacharya KG, Wang J, et al. 20S-hydroxyvitamin D3, noncalcemic product of CYP11A1 action on vitamin D3, exhibits potent antifibrogenic activity in vivo. J Clin Endocrinol Metab 2013; 98: E298-303; PMID:23295467; http://dx.doi.org/10.1210/jc.2012-3074.
72. Smith LL. Another cholesterol hypothesis: cholesterol as antioxidant. Free Radic Biol Med 1991; 11: 47-61; PMID:1937129; http://dx.doi.org/10.1016/ 0891-5849(91)90187-8.
73. Wiseman H. Vitamin D is a membrane antioxidant. Ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol, ergosterol and tamoxifen and relevance to anticancer action. FEBS Lett 1993; 326: 285-8; PMID:8325381; http://dx.doi.org/10.1016/0014-5793(93)81809-E.
74. Tan DX, Manchester LC, Hardeland R, Lopez-Burillo S, Mayo JC, Sainz RM, et al. Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J Pineal Res 2003; 34: 75-8; PMID:12485375; http://dx.doi.org/10.1034/j.1600-079X.2003.02111.x.
75. Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM, et al. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chem 2002; 2: 181-97; PMID:11899100; http://dx.doi.org/10.2174/1568026023394443.
76. Tan DX, Manchester LC, Burkhardt S, Sainz RM, Mayo JC, Kohen R, et al. N1-acetyl-N2-formyl-5- methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant. FASEB J 2001; 15: 2294-6; PMID:11511530.
77. Slominski A, Tobin DJ, Zmijewski MA, Wortsman J, Paus R. Melatonin in the skin: synthesis, metabolism and functions. Trends Endocrinol Metab 2008; 19: 17-24; PMID:18155917; http://dx.doi.org/10.1016/j.tem.2007.10.007.
78. Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, Ostrom RS, Slominski AT. Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol 2012; 351: 152-66; PMID:22245784; http://dx.doi.org/10.1016/j.mce.2012.01.004.
79. Fischer TW, Slominski A, Zmijewski MA, Reiter RJ, Paus R. Melatonin as a major skin protectant: from free radical scavenging to DNA damage repair. Exp Dermatol 2008; 17: 713-30; PMID:18643846; http://dx.doi.org/10.1111/j.1600-0625. 2008.00767.x.
80. Fischer TW, Sweatman TW, Semak I, Sayre RM, Wortsman J, Slominski A. Constitutive and UV-induced metabolism of melatonin in keratinocytes and cell-free systems. FASEB J 2006; 20: 1564-6; PMID:16793870; http://dx.doi.org/ 10.1096/fj.05-5227fje.
81. Slominski A, Wortsman J, Tobin DJ. The cutaneous serotoninergic/ melatoninergic system: securing a place under the sun. FASEB J 2005; 19: 176-94; PMID:15677341; http://dx.doi.org/10.1096/fj.04-2079rev.
82. Pisarchik A, Slominski AT. Alternative splicing of CRH-R1 receptors in human and mouse skin: identification of new variants and their differential expression. FASEB J 2001; 15: 2754-6; PMID:11606483.