Biological activities of apo-canthaxanthinoic acids related to gap junctional communication

Apo-carotenoids with different numbers of conjugated double bonds are forme d upon excentric cleavage of carotenoids, These compounds may exhibit biolo gical activities similar to those of the parent carotenoids or their centra l cleavage products, the retinoids, 11-Apo-canthaxanthin-11-oic acid, 13-ap o-canthaxanthin-13-oic acid, and 14'-apo-canthaxanthin-14'-oic acid, carryi ng 2, 3, or 5 conjugated double bonds in the polyene chain, respectively, w ere tested for their effects on gap junctional communication (GJC), on stab ilization of connexin43 mRNA, and on the activation of the retinoic acid-be ta 2 receptor (RAR-beta 2 receptor); the effects mere compared to those of retinoic acid and 4-oxo-retinoic acid, known to stimulate GJC and to activa te the RAR-beta 2 receptor. The effects of 4-oxo-retinoic acid were compara ble to those of retinoic acid. 4-Oxo-retinoic acid, like retinoic acid, inf luences the stability of connexin 43 mRNA via elements located in the 3'-UT R. No effects were observed with the short-chain apo-canthaxanthinoic acids . A small but statistically significant induction of GJC and transactivatio n activity towards the RAR beta 2 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 rel ated to activities mediated by the products of the central cleavage, (C) 19 99 Academic Press.