Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses.

Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Research Abstract Details 

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Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Abstract Text:

Ouliana Ziouzenkova,Gabriela Orasanu,Galina Sukhova,Evan Lau,Joel P Berger,Guangwen Tang,Norman I Krinsky,Gregory G Dolnikowski,Jorge Plutzky,

beta-Carotene and its metabolites exert a broad range of effects, in part by regulating transcriptional responses through specific nuclear receptor activation. Symmetric cleavage of beta-carotene can yield 9-cis retinoic acid (9-cisRA), the natural ligand for the nuclear receptor RXR, the obligate heterodimeric partner for numerous nuclear receptor family members. A significant portion of beta-carotene can also undergo asymmetric cleavage to yield apocarotenals, a series of poorly understood naturally occurring molecules whose biologic role, including their transcriptional effects, remains essentially unknown. We show here that beta-apo-14'-carotenal (apo14), but not other structurally related apocarotenals, represses peroxisome proliferator-activated receptors (PPAR) and RXR activation and biologic responses induced by their respective agonists both in vitro and in vivo. During adipocyte differentiation, apo14 inhibited PPARgamma target gene expression and adipogenesis, even in the presence of the potent PPARgamma agonist BRL49653. Apo14 also suppressed known PPARalpha responses, including target gene expression and its known antiinflammatory effects, but not if PPARalpha agonist stimulation occurred before apo14 exposure and not in PPARalpha-deficient cells or mice. Other apocarotenals tested had none of these effects. These data extend current views of beta-carotene metabolism to include specific apocarotenals as possible biologically active mediators and identify apo14 as a possible template for designing PPAR and RXR modulators and better understanding modulation of nuclear receptor activation. These results also suggest a novel model of molecular endocrinology in which metabolism of a parent compound, beta-carotene, may alternatively activate (9-cisRA) or inhibit (apo14) specific nuclear receptor responses.

Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Publishing Authors By Initials

O Ziouzenkova,G Orasanu,G Sukhova,E Lau,JP Berger,G Tang,NI Krinsky,GG Dolnikowski,J Plutzky,

For similar organic chemicals: hydrocarbons: hydrocarbons, acyclic: alkenes: polyenes: carotenoids: beta carotene research abstracts see: organic chemicals: hydrocarbons: hydrocarbons, acyclic: alkenes: polyenes: carotenoids: beta carotene research

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Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular endocrinology (Baltimore, Md.)

VOLUME: 21

Page Numbers: 77-88

Journal Abbreviation: Mol. Endocrinol.

ISSN: 0888-8809

DAY: 28

MONTH: 09

YEAR: 2006

Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8801431

Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Keywords Mesh Terms:

KEYWORDS: beta Carotene

MESH TERMS: chemistry

Chemical & Substance for Abstract: Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Information

Substance Name: beta Carotene

Registry Number: 7235-40-7

Grant and Affiliation Information for Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses.

AFFILIATION: Cardiovascular Division, Brigham and Women's Hospital, Havard University, Boston, Massachusetts 02115, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL071745

ACRONYM: HL

MEDLINETA: Mol Endocrinol

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