Astaxanthin diminishes gap junctional intercellular communication in primary human fibroblasts.
Astaxanthin is a carotenoid found in plants and algae; it provides the color of marine seafood such as salmon, lobster, or shrimp. Carotenoids are antioxidants and exhibit other biological functions, including effects on gap junctional communication important for homeostasis, growth control, and development of cells. Cancer cells have an impaired gap junctional intercellular communication. The objective of the present study was to determine the effects of astaxanthin and canthaxanthin on gap junctional intercellular communication in vitro. Primary human skin fibroblasts were exposed to carotenoids from 0.001 to 10 micromol/L, and gap junctional communication was measured with a dye transfer assay. After incubation with canthaxanthin for 24 and 72 h, intercellular communication increased, whereas it was strongly diminished by astaxanthin at levels > 0.1 micromol/L. Inhibition was reversed when astaxanthin was withdrawn. Western blot analysis showed that after exposure to canthaxanthin, the amount of the gap junction protein connexin43 was increased. Incubation with astaxanthin led to a change in the phosphorylation pattern of connexin43, shifting from higher to lower phosphorylation states. We suggest that astaxanthin affects channel function by changing the phosphorylation pattern of connexin43.
Daubrawa
Felicitas
F
Institute of Biochemistry and Molecular Biology I, Heinrich-Heine-University Düsseldorf, D-40001 Düsseldorf, Germany.
Sies
Helmut
H
Stahl
Wilhelm
W
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects*; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D018031:Connexin 43 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D017629:Gap Junctions / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D010766:Phosphorylation; D024341:Xanthophylls; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D018031:Connexin 43; D024341:Xanthophylls; D019207:beta Carotene; C005948:astaxanthine