Stimulation of gap junctional communication: comparison of acyclo-retinoic acid and lycopene.
Carotenoids and retinoids stimulate gap junctional communication (GJC), thought to be related to cancer-preventive properties. Lycopene, a nonprovitamin A carotenoid and its possible oxidation product, acyclo-retinoic acid, were tested for their effect on GJC, on stabilization of connexin43 mRNA, and on the transactivation of the RAR-beta2-promoter in vitro. In human fetal skin fibroblasts, GJC was stimulated by lycopene and acyclo-retinoic acid. Lycopene was effective at a concentration of 0.1 microM, whereas higher amounts of acyclo-retinoic acid (1 microM) were needed for comparable stimulation. Stabilizing effects of acyclo-retinoic acid on the mRNA of connexin43 via elements located in the 3'-UTR were weak. In comparison to retinoic acid (0.1 microM), considerably higher concentrations of the acyclo analog (50 microM) were required for similar effects; lycopene (0.1 microM) was not active in this system. Likewise, unphysiologically high levels of acyclo-retinoic acid (50 microM) were necessary to transactivate the RAR-beta2 promoter. The data demonstrate that acyclo-retinoic acid is much less active than retinoic acid with respect to GJC and retinoid-related signaling. Therefore, we conclude that lycopene affects GJC independent of the formation of acyclo-retinoic acid.
Stahl
W
W
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, D-40001, Germany. wilhelm.stahl@uni-duesseldorf.de
von Laar
J
J
Martin
H D
HD
Emmerich
T
T
Sies
H
H
D002338:Carotenoids / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D000077276:Lycopene; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
D018031:Connexin 43; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D002338:Carotenoids; D014212:Tretinoin; D000077276:Lycopene