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DHCR24: Unexpected new directions for a terminal step in cholesterol synthesis
Author(s) -
Zerenturk Eser,
Sharpe Laura J,
Kristiana Ika,
Brown Andrew J
Publication year - 2013
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.27.1_supplement.822.2
Subject(s) - cholesterol , sterol regulatory element binding protein , cholesterol synthesis , sterol , biology , hmg coa reductase , reductase , steroid , hormone , endogeny , microbiology and biotechnology , enzyme , biochemistry , endocrinology
Cholesterol is necessary for mammalian life, as an essential component in cell membranes, foetal development, and a precursor for steroid hormones. Hence, cholesterol levels must be tightly regulated. Previous research has focused on an early step in cholesterol synthesis: HMG‐CoA reductase, target of the cholesterol‐lowering statin drugs. However, less is known about other steps in the pathway. We investigated 3β‐hydroxysterol Δ24‐reductase (DHCR24), involved in the last step of cholesterol synthesis, and implicated in inflammation, oxidative stress and HCV infection. We show that DHCR24 is regulated at multiple levels, with potent effects on cholesterol synthesis. We found regulation through dual sterol regulatory elements (SREs) within the DHCR24 promoter, which work cooperatively to regulate expression, and show that endogenous side‐chain oxysterols, in particular 24( S ),25‐epoxycholesterol (24,25EC), directly inhibit DHCR24 activity. These findings indicate DHCR24 may be an important regulatory step in cholesterol synthesis and maintaining cellular cholesterol homeostasis. This research is supported by the National Health and Medical Research Council and National Heart Foundation of Australia.