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12‐ O ‐Tetradecanoylphorbol 13‐Acetate and Fibroblast Growth Factor Increase the 30‐kDa Substrate Binding Subunit of Type II Deiodinase in Astrocytes
Author(s) -
Len Ana Maria,
Esfandiari All,
Gavaret JeanMichel,
Courtin Françoise,
Pierre Michel
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.62062116.x
Subject(s) - deiodinase , 12 o tetradecanoylphorbol 13 acetate , fibroblast growth factor , protein subunit , intracellular , fibroblast , chemistry , growth factor , biochemistry , medicine , microbiology and biotechnology , endocrinology , receptor , enzyme , triiodothyronine , biology , in vitro , hormone , protein kinase c , phorbol ester , gene
Type II 5′‐deiodinase (D‐II) catalyzes the intracellular conversion of thyroxine (T 4 ) to 3,5,3′‐triiodothyronine (T 3 ) in the brain., The D‐II activity in astroglial cell cultures is induced by several pathways including cyclic AMP (cAMP), 12‐ O ‐tetradecanoylphorbol 13‐acetate (TPA), and fibroblast growth factors (FGFs). We have examined the effect of TPA and FGFs on the 30‐kDa substrate binding subunit of D‐II, by affinity labeling with N ‐bromoacetyl‐[ 128 I]T 4 in astroglial cells. TPA (0.1 μ M ), 20 ng/ml acidic FGF (aFGF), and 1 m M 8‐bromo cyclic AMP all caused an increase in the 30‐kDa protein. cAMP induced the greatest increase (fivefold) followed by TPA (3.2‐fold) and FGF (2.8‐fold). Glucocorticoids acted synergistically with cAMP and aFGF and promoted the effect of TPA. Affinity labeling was competitively inhibited by bromoacetyl‐T 4 > bromoacetyl‐T 3 > T 4 > reverse T 3 > iopanoic acid > T 3 > 3,5,3‐triiodothyroacetic acid. The effect of TPA (0.1 μ M ) was maximum at 8 h and then gradually decreased. aFGF (20 ng/ml) plus heparin (17 μg/ml) induced a maximal 30‐kDa increase at 8 h, which stayed stable for up to 24 h. The effect of aFGF was concentration dependent. Of the other growth factors studied, only basic FGF and platelet‐derived growth factor induced small increases in the 30‐kDa protein. Epidermal growth factor had little effect. In vitro labeling of cAMP, TPA, and aFGF‐stimulated cell sonicates resulted in an increase in the 30‐kDa protein that paralleled the increase in D‐II activity. These results correlate well with our previous studies showing that several distinct signaling pathways regulate D‐II activity. They suggest that the regulation of D‐II in astrocytes by cAMP, TPA, and aFGF involves an accumulation of the 30‐kDa substrate binding subunit.