A transgenic reporter mouse model for assessment of retinoic acid receptor transcriptional activation.

Vitamin A is essential for a wide range of life processes throughout embryogenesis to adult life. With the aim of developing an model to monitor retinoic acid receptor (RAR) transactivation real-time in intact animals, we generated transgenic mice carrying a luciferase (luc) reporter gene under the control of retinoic acid response elements (RAREs) consisting of three copies of a direct repeat with five spacing nucleotides (DR5). : Transgenic mice carrying a RARE dependent luciferase reporter flanked with insulator sequence were generated by pronuclear injection.

Apo-14´-Carotenoic Acid Is a Novel Endogenous and Bioactive Apo-Carotenoid.

Carotenoids can be metabolized to various apo-carotenoids and retinoids. Apo-15´-carotenoic acid (retinoic acid, RA) is a potent activator of the retinoic acid receptor (RAR) in its all-- (ATRA) and 9- (9CRA) forms. In this study we show firstly, that apo-14´-carotenoic acid (A14CA), besides retinoic acids, is present endogenously and with increased levels in the human organism after carrot juice supplementation rich in β-carotene.

A Review About Lycopene-Induced Nuclear Hormone Receptor Signalling in Inflammation and Lipid Metabolism via still Unknown Endogenous Apo-10´-Lycopenoids.

Lycopene is the red pigment in tomatoes and tomato products and is an important dietary carotenoid found in the human organism. Lycopene-isomers, oxidative lycopene metabolites and apo-lycopenoids are found in the food matrix. Lycopene intake derived from tomato consumption is associated with alteration of lipid metabolism and a lower incidence of cardiovascular diseases (CVD).

Lycopene supplementation restores vitamin A deficiency in mice and possesses thereby partial pro-vitamin A activity transmitted via RAR signaling.

Scope: The aim of this study was to compare if lycopene also possesses pro-vitamin A (VA) activity comparable to known VA derivatives.

Materials And Methods: We used a transgenic retinoic acid response element reporter mouse model (n = 8, per group) for this study, and after the initial wash out of VA using a vitamin A deficient diet (VAD) for 18 weeks, the animals were supplemented further with (a) VAD-fed mice, (b) VAD-fed mice plus retinol (20 mg/kg bw), (c) VAD-fed mice plus β-carotene (40 mg/kg bw), and (d) VAD-fed mice plus lycopene (40 mg/kg bw). Using ex vivo scanning and gene expression analysis of retinoid target and VA marker gene analysis in various organs of these supplemented mice (b, c, d), we found increased luciferase activity and normalized marker and target gene analysis compared to group a.

Lycopene-derived bioactive retinoic acid receptors/retinoid-X receptors-activating metabolites may be relevant for lycopene's anti-cancer potential.

Dietary consumption of tomato products and especially the red tomato pigment lycopene has been associated with lower risk of cancer. New evidence is emerging toward metabolic pathways mediating the anti-cancer activities of lycopene. In this review, we explore associations between tomatoes and lycopene intake and cancer and relate this to the metabolic activation pathways of lycopene via carotene oxygenases and further carotenoid/retinoid-metabolizing enzymes to apo-lycopenoids.

Reduced retinoid signaling in the skin after systemic retinoid-X receptor ligand treatment in mice with potential relevance for skin disorders.

Retinoid-X receptor (RXR)- and retinoic acid receptor (RAR)-mediated signaling is induced by retinoic acids (RA), which are involved in the regulation of skin permeability, differentiation and immune response. Dysregulation of retinoid signaling is present in various skin disorders. Topically and systemically administered synthetic RAR or RXR agonists might influence retinoid-mediated signaling in the skin of RARE reporter animals and gene expression analysis for retinoid, skin homeostasis and skin inflammation marker genes and local retinoid concentrations.

Lycopene induces retinoic acid receptor transcriptional activation in mice.

Scope: Lycopene is a lipophilic carotenoid and provides the red colour to tomatoes and tomato product. Various studies indicated that lycopene and tomatoes/tomato products are able to positively influence various diseases associated with a chronic inflammation. The mechanism of action of lycopene to elicit these effects is partly unknown.

Organic synthesis of new putative lycopene metabolites and preliminary investigation of their cell-signaling effects.

Tomato is the main dietary source of lycopene, a carotenoid that is known to have protective effects on health and whose metabolites could also be involved in bioactivity. Herein we present the first organic synthesis of two potentially bioactive lycopene metabolites, namely, 10'-apolycopen-10'-oic acid (6) and 14'-apolycopen-14'-oic acid (13), which were obtained in their (all-E) stereoisomeric forms using Wittig and Horner-Wadsworth-Emmons type coupling reactions. Both molecules are shown to up-regulate the carotenoid asymmetric cleavage enzyme BCO2 while having no effect on BCO1 expression.