Thyroid hormone-regulated brain mitochondrial genes revealed by differential cDNA cloning.
AUTOR(ES)
Vega-Núñez, E
RESUMO
Thyroid hormone (T3) plays a critical role in the development of the central nervous system and its deficiency during the early neonatal period results in severe brain damage. However the mechanisms involved and the genes specifically regulated by T3 during brain development are largely unknown. By using a subtractive hybridization technique we have isolated a number of cDNAs that represented mitochondrial genes (12S and 16S rRNAs and cytochrome c oxidase subunit III). The steady state level of all three RNAs was reduced in hypothyroid animals during the postnatal period and T3 administration restored control levels. During fetal life the level of 16S rRNA was decreased in the brain of hypothyroid animals, suggesting a prenatal effect of thyroid hormone on brain development. Since T3 does not affect the amount of mitochondrial DNA, the results suggest that the effect of T3 is at transcriptional and/or postranscriptional level. In addition, the transcript levels for two nuclear-encoded mitochondrial cytochrome c oxidase subunits: subunits IV and VIc were also decreased in the brains of hypothyroid animals. Hypothyroidism-induced changes in mitochondrial RNAs were followed by a concomitant 40% decrease in cytochrome c oxidase activity. This study shows that T3 is an important regulator of mitochondrial function in the neonatal brain and, more importantly, provides a molecular basis for the specific action of this hormone in the developing brain.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=185276Documentos Relacionados
- Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line.
- Thyroid hormone-regulated enhancer blocking: cooperation of CTCF and thyroid hormone receptor
- Study of a growth hormone-regulated protein secreted by rat hepatocytes: cDNA cloning, anti-protease activity and regulation of its synthesis by various hormones.
- Structure of rat DNA polymerase beta revealed by partial amino acid sequencing and cDNA cloning.
- A thyroid hormone-regulated gene in Xenopus laevis encodes a type III iodothyronine 5-deiodinase.