Effect of retinoids on protein kinase C activity and on the binding characteristics of the tri-iodothyronine nuclear receptor.
Retinoids and thyroid hormones exert profound effects on the development, growth and homeostasis of vertebrates. The receptor proteins which bind retinoic acid, tri-iodothyronine (T3) or steroid hormones and, as a result of this binding, interact with DNA to stimulate expression of specific genes, belong to the same recently discovered superfamily. The functionality of thyroid and steroid hormone receptors is thought to be related to a phosphorylation-dephosphorylation cycle. In the present work, the action of two retinoids (retinol and retinoic acid) was studied on the properties of T3-nuclear receptors and on protein kinase C (PKC) activity in the rat liver (PKC is known to be a phosphorylating enzyme for various proteins). The influence of 12-O-tetradecanoyl phorbol-13-acetate (TPA; known to enhance PKC activity) on the properties of T3-nuclear receptors was also investigated. Measurements of binding characteristics and enzyme activity were performed 4 or 12 h after a single i.p. injection of retinol or retinoic acid (6 mg/kg body weight) or 1 h after a single i.p. injection of TPA (0.7 mg/kg). The activity of PKC was increased 4 h after administration of the retinoids, and the affinity of the T3-nuclear receptor protein was increased markedly after 12 h. The activity of PKC and the affinity of nuclear T3 receptor were both increased 1 h after administration of TPA. These observations provide indirect evidence that retinoids, particularly retinoic acid, induce an increase in PKC activity and a subsequent increase in the affinity of the T3-nuclear receptor protein.
Pailler-Rodde
I
I
Département Alimentation et Nutrition, Université de Bordeaux, Talence, France.
Garcin
H
H
Higueret
P
P
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D012176:Retinoids / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism*; D014801:Vitamin A / Q000494:pharmacology
D011988:Receptors, Thyroid Hormone; D012176:Retinoids; D014284:Triiodothyronine; D014801:Vitamin A; D014212:Tretinoin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate