TRIIODOTHYRONINE HAS DIVERSE AND MULTIPLE STIMULATING EFFECTS ON EXPRESSION OF THE MAJOR MYELIN PROTEIN GENES

被引:85
作者
TOSIC, M [1 ]
TORCH, S [1 ]
COMTE, V [1 ]
DOLIVO, M [1 ]
HONEGGER, P [1 ]
MATTHIEU, JM [1 ]
机构
[1] UNIV LAUSANNE, INST PHYSIOL, CH-1000 LAUSANNE 17, SWITZERLAND
关键词
TRIIODOTHYRONINE; MYELIN BASIC PROTEIN; PROTEOLIPID PROTEIN; MYELIN ASSOCIATED GLYCOPROTEIN; 2'; 3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE;
D O I
10.1111/j.1471-4159.1992.tb11009.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
If the importance of triiodothyronine (T3) 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 T3 on the expression of myelin protein genes in aggregating brain cell cultures. T3 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). T3 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 T3 increases Mag and Cnp transcription rates. After inhibiting transcription with actinomycin D, we measured the half-lives of specific mRNAs. Our results show that T3 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 T3 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 T3 stimulation of myelin protein genes.
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页码:1770 / 1777
页数:8
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