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Cholecalciferol increases 7‐dehydrocholesterol reductase activity in adult human epidermal keratinocytes
Author(s) -
Zou Ling,
Porter Todd D
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.787.6
Subject(s) - hacat , cholecalciferol , calcitriol , endocrinology , vitamin d and neurology , medicine , chemistry , biology , biochemistry , in vitro
7‐Dehydrocholesterol reductase (DHCR7) catalyzes the final step in cholesterol synthesis by reducing the 7–8 double bond of 7‐dehydrocholesterol. In skin cells 7‐dehydrocholesterol also can be converted to cholecalciferol (vitamin D3) by ultraviolet radiation, providing a second pathway for 7‐dehydrocholesterol metabolism in these cells. We hypothesized that keratinocytes might regulate cholecalciferol levels by modulating the activity of DHCR7, a hypothesis supported by evidence that DHCR7 is a phosphoprotein, and is activated by the addition of ATP to liver microsomes. To test this hypothesis, DHCR7 activity was measured in lysates of rat hepatoma cells (McA‐RH7777), immortalized human keratinocytes (HaCaT), and adult human epidermal keratinocytes (HEKa) after treatment of the cells with cholecalciferol or calcitriol for 3 h. Cholecalciferol had no effect on DHCR7 activity in hepatoma cells or HaCaT cells, but increased DHCR7 activity in HEKa cells by 3‐fold at 1 μM and 4‐fold at 10 μM. Calcitriol (100 nM), the active form of vitamin D, had no effect on DHCR7 activity in HaCaT cells at 3 or 24 h, but decreased DHCR7 activity in HEKa cells after 3 h by 40%. These findings suggest that cholecalciferol regulates its own levels in keratinocytes by increasing the activity of DHCR7, thereby decreasing the levels of the cholecalciferol precursor, 7‐dehydrocholesterol.