The goal of this research program is to develop a better understanding about how vitamin D3 is made and processed in the skin. During the past four years, we have accomplished the major Specific Aims that we had proposed in our last grant period and established a very sensitive high performance liquid chromatography methodology that will be important for continuing studies on the photobiology of previtamin D and vitamin D3. Ten photoproducts of previtamin D3 and six photoproducts of vitamin D3 have now been identified after exposure to ultraviolet radiation that is comparable to human exposure levels. We plan to study the photoproduction of toxisterols and suprasterols in a liposomal model and human skin equivalent, and in cultured human keratinocytes and human skin. The biologic activity of the various toxisterols and suprasterols will be investigated in cultured human keratinocytes with specific emphasis on regulation of cellular proliferation and terminal differentiation. In addition, we will evaluate the metabolism of the most prominent toxisterols and sprasterols that are produced in the skin. This will be accomplished by making tritium-labeled toxisterols and sprasterols, and evaluating their metabolism in cultured human keratinocytes. Results from this study should provide important new insights into the photoproduction of toxisterols and suprasterols in human skin and provide new information about their potential biologic functions in the skin.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR036963-16
Application #
6738984
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Program Officer
Moshell, Alan N
Project Start
1987-09-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
16
Fiscal Year
2004
Total Cost
$383,050
Indirect Cost
Name
Boston University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Holick, Michael F (2014) Sunlight, ultraviolet radiation, vitamin D and skin cancer: how much sunlight do we need? Adv Exp Med Biol 810:1-16
Karsten, Kristopher B; Ferguson, Gary W; Chen, Tai C et al. (2009) Panther chameleons, Furcifer pardalis, behaviorally regulate optimal exposure to UV depending on dietary vitamin D3 status. Physiol Biochem Zool 82:218-25
Holick, Michael F (2009) Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 19:73-8
Holick, Michael F (2008) The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med 29:361-8
Holick, Michael F (2008) Vitamin D: a D-Lightful health perspective. Nutr Rev 66:S182-94
Holick, Michael F (2008) Sunlight, UV-radiation, vitamin D and skin cancer: how much sunlight do we need? Adv Exp Med Biol 624:1-15
Chen, Tai C; Chimeh, Farhad; Lu, Zhiren et al. (2007) Factors that influence the cutaneous synthesis and dietary sources of vitamin D. Arch Biochem Biophys 460:213-7
Holick, Michael F; Chen, Tai C; Lu, Zhiren et al. (2007) Vitamin D and skin physiology: a D-lightful story. J Bone Miner Res 22 Suppl 2:V28-33
Holick, Michael F (2007) Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs Aging 24:1017-29
Holick, Michael F (2007) Vitamin D deficiency. N Engl J Med 357:266-81

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