title: Biological activities of Apo-canthaxanthinoic acids related to gap junctional communication.
abstract: Apo-carotenoids with different numbers of conjugated double bonds are formed upon eccentric cleavage of carotenoids. These compounds may exhibit biological activities similar to those of the parent carotenoids or their central cleavage products, the retinoids. 11-Apo-canthaxanthin-11-oic acid, 13-apo-canthaxanthin-13-oic acid, and 14'-apo-canthaxanthin-14'-oic acid, carrying 2, 3, or 5 conjugated double bonds in the polyene chain, respectively, were tested for their effects on gap junctional communication (GJC), on stabilization of connexin43 mRNA, and on the activation of the retinoic acid-beta2 receptor (RAR-beta2 receptor); the effects were compared to those of retinoic acid and 4-oxo-retinoic acid, known to stimulate GJC and to activate the RAR-beta2 receptor. The effects of 4-oxo-retinoic acid were comparable to those of retinoic acid. 4-Oxo-retinoic acid, like retinoic acid, influences the stability of connexin 43 mRNA via elements located in the 3'-UTR. No effects were observed with the short-chain apo-canthaxanthinoic acids. A small but statistically significant induction of GJC and transactivation activity towards the RARbeta2 was found with 14'-apo-canthaxanthin-14'-oic acid. This might be due to biological effects of the compound itself or to biologically active breakdown products. The data suggest that the major biological effects of canthaxanthin on retinoid signaling pathways are related to activities mediated by the products of the central cleavage.
authors.affiliation: Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, D-40001, Germany.
authors.forename: V B
authors.initials: VB
authors.lastname: Teicher
authors.forename: N
authors.initials: N
authors.lastname: Kucharski
authors.forename: H D
authors.initials: HD
authors.lastname: Martin
authors.forename: P
authors.initials: P
authors.lastname: van der Saag
authors.forename: H
authors.initials: H
authors.lastname: Sies
authors.forename: W
authors.initials: W
authors.lastname: Stahl
mesh_terms: D016644:Canthaxanthin / Q000494:pharmacology*; D002338:Carotenoids / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D018031:Connexin 43 / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D017629:Gap Junctions / Q000187:drug effects*; D006801:Humans; D012323:RNA Processing, Post-Transcriptional; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology; D012867:Skin / Q000166:cytology; D015533:Transcriptional Activation
chemical_list: D018031:Connexin 43; D018168:Receptors, Retinoic Acid; D012176:Retinoids; C082925:retinoic acid receptor beta; D002338:Carotenoids; D016644:Canthaxanthin