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Triiodothyronine Has Diverse and Multiple Stimulating Effects on Expression of the Major Myelin Protein Genes
Author(s) -
Tosic Mirjana,
Torch Sakina,
Comte Véronique,
Dolivo Michel,
Honegger Paul,
Matthieu JeanMarie
Publication year - 1992
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 - 10.1111/j.1471-4159.1992.tb11009.x
Subject(s) - proteolipid protein 1 , myelin , myelin basic protein , myelin proteolipid protein , biology , gene expression , messenger rna , microbiology and biotechnology , transcription (linguistics) , oligodendrocyte , gene , biochemistry , endocrinology , central nervous system , linguistics , philosophy
If the importance of triiodothyronine (T 3 ) on brain development including myelinogenesis has long been recognized, its mechanism of action at the gene level is still not fully elucidated. We studied the effect of T 3 on the expression of myelin protein genes in aggregating brain cell cultures. T 3 increases the concentrations of mRNA transcribed from the following four myelin protein genes: myelin basic protein ( Mbp ), myelin‐associated glycoprotein ( Mag ), proteolipid protein ( Plp ), and 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase ( Cnp ). T 3 is not only a triggering signal for oligodendrocyte differentiation, but it has continuous stimulatory effects on myelin gene expression. Transcription in isolated nuclei experiments shows that T 3 increases Mag and Cnp transcription rates. After inhibiting transcription with actinomycin D, we measured the half‐lives of specific mRNAs. Our results show that T 3 increases the stability of mRNA for myelin basic protein, and probably proteolipid protein. In vitro translation followed by myelin basic protein‐specific immunoprecipitation showed a direct stimulatory effect of T 3 on myelin basic protein mRNA translation. Moreover, this stimulation was higher when the mRNA was already stabilized in culture, indicating that stabilization is achieved through mRNA structural modifications. These results demonstrate the diverse and multiple mechanisms of T 3 stimulation of myelin protein genes.