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Regulation of Peroxisome Proliferator-Activated Receptor Alpha by Selected Beta-Apocarotenoids

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Degree
Master of Science, Ohio State University, Human Ecology: Human Nutrition and Food Management, .
Abstract
β-carotene is a prominent human dietary carotenoid known for its provitamin A and antioxidant properties. In addition to these functions, eccentric cleavage of β-carotene at double bonds on the polyene chain other than the 15-15’ central double bond by autooxidation or the cytosolic enzyme β,β-carotene 9’,10’-oxygenase (BCO2) produces β-apocarotenoids of varying chain lengths that could have important biological roles. Long chain β-apocarotenoids share some structural characteristics similar to natural and synthetic ligands of peroxisome proliferator-activated receptor alpha (PPARα), a member of the steroid/retinoid nuclear receptor family. PPARα is known to have a vital role in lipid utilization, lipoprotein metabolism, and inflammatory responses. Therefore, we hypothesized that β-apocarotenoids can regulate gene expression by activating PPARα. Transactivation assays were performed using the COS-1 cell line transfected with PPARα nuclear receptor vector and treated with β-cyclogeranic acid (BCA), β-cyclocitral (BCL), β-ionylideneacetaldehyde (BIA), β-ionylideneacetic acid (BIAA), β-apo-13’-carotenone (C13 ketone), β-apo-8’-carotenal (CAL)/ carotenoic acid (CA), β-apo-12’-CAL/CA, or β-apo-14’-CAL/CA. The synthetic fibrate GW0742 was used as a positive control. We found that cells treated with BCL, β-apo-8’-CAL/CA, BIA, BIAA, β-apo-12’-CAL, and β-apo-14’-CAL did not activate PPARα. Administration of BCA, β-apo-12’-CA, C13 ketone, and β-apo-14’-CA to the cells resulted increased PPARα activity suggesting these β-apocarotenoids may function as PPARα agonists in vitro.
Subject Headings
Nutrition
Keywords
β-apocarotenoids; PPARα
Committee / Advisors
Earl Harrison, PhD (Advisor)
Ouliana Ziouzenkova, PhD (Committee Member)
Steven Schwartz, PhD (Committee Member)

Document number: osu1275401911
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