Stimulation of gap junctional intercellular communication by thalidomide and thalidomide analogs in human fetal skin fibroblasts (HFFF2) and in rat liver epithelial cells (WB-F344).
Gap junction channels maintain cell-cell communication and are essential for the coordination of tissues, playing a pivotal role in embryonal development. Gap junctional intercellular communication (GJIC), studied here in human fetal skin fibroblasts (HFFF2) and in rat liver epithelial cells (WB-F344), was almost doubled upon exposure to thalidomide (10 microM) in the presence of NADH or NADPH (20 microM). Neither in HFFF2 nor in WB-F344 cells did any detectable alteration in GJIC occur with the thalidomide analog EM 16 (10 microM), known as a non-teratogenic compound. The thalidomide analog EM 364 (10 microM) increased GJIC without prior metabolic activation. It is suggested that GJIC modification may be related to the pharmacological and toxicological properties of thalidomide.
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Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Postfach 101007, D-40001, Düsseldorf, Germany.
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D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003067:Coenzymes / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000166:cytology; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors
D020533:Angiogenesis Inhibitors; D003067:Coenzymes; C001079:2-(2,6-dioxopiperidin-3-yl)phthalimidine; D013792:Thalidomide