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Potential roles of β‐apo‐carotenoids on activation of retinoic acid receptors
Author(s) -
Marsh Rebekah S,
Yan Yan,
Reed Vanessa M,
Hruzkewycz Damian,
Curley Robert W,
Harrison Earl H
Publication year - 2009
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.23.1_supplement.730.3
Subject(s) - carotenoid , retinoic acid , retinoic acid receptor , transactivation , biochemistry , chemistry , polyene , receptor , luciferase , transfection , transcription factor , gene
β‐Carotene oxygenase 2 catalyzes the cleavage of β‐carotene at non‐central double bonds of the polyene chain, yielding apo‐carotenals. The biological roles and the potential regulation of retinoic acid receptors (RARs) by apo‐carotenoids are not clear. The hypothesis we seek to test is that apo‐carotenoids are able to stimulate transcription by activation of RARs. We will test the effects of all of the long and short chain apo‐carotenals arising from eccentric cleavage of β‐carotene (and the corresponding apo‐carotenoic acids) on the activation of RARα or RARβ transfected into monkey kidney cells along with RARE‐ luciferase reporter constructs. So far, we have obtained or synthesized apo‐8′‐carotenoic acid, apo‐14′‐carotenoic acid, β‐cyclocitral, β‐cyclogernaic acid, β‐ionylideneacetaldehyde, β‐ionylideneacetic acid, β‐ionone, and a C13 ketone. None of these apo‐carotenoids showed significant transactivation activity for RARs when compared to all‐trans retinoic acid (RA). The results suggest that the biological effects of these apo‐carotenoids are through mechanisms other than activation of RARα and β. Supported by NIH grants DK044498 and HL049879.