Identification of the Mitochondrial NADH Dehydrogenase Subunit-3 as a Thyroid Hormone-Regulated Gene by Whole Genome PCR Analysis

Iglesias, Teresa; Caubín, J.; Zaballos, Ángel; Bernal, Juan; Múñoz, Alberto

doi:10.1006/bbrc.1995.1755

Cited by 56 publications

(31 citation statements)

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“…In mammals, neonatal hypothyroidism results in decreased brain oxidative phosphorylation (73) and alterations in mitochondrial morphology (74). Recent reports in rat and mouse show that the expression of several mitochondrial genes is altered by thyroid status in neonatal animals (53,54,75). Another energy-converting enzyme identified in this screen is brain-type CK.…”

Section: Identification Of T 3 -Regulated Neuralmentioning

confidence: 79%

“…Several attempts to isolate T 3 -regulated genes in neonatal rodent brain by differential screening methods have met with limited success (52)(53)(54). Using subtractive hybridization, Munoz et al (52) identified two cDNAs corresponding to T 3 -regulated mRNAs that were decreased only 2-fold in brains from hypothyroid rats; one of these was tentatively identified as myelin basic protein, whereas the other was not identified.…”

Section: Identification Of T 3 -Regulated Neuralmentioning

confidence: 99%

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Thyroid Hormone-dependent Gene Expression Program for Xenopus Neural Development

Denver

Pavgi

Shi

1997

Journal of Biological Chemistry

126

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Although thyroid hormone (TH) plays a significant role in vertebrate neural development, the molecular basis of TH action on the brain is poorly understood. Using polymerase chain reaction-based subtractive hybridization we isolated 34 cDNAs for TH-regulated genes in the diencephalon of Xenopus tadpoles. Northern blots verified that the mRNAs are regulated by TH and are expressed during metamorphosis. Kinetic analyses showed that most of the genes are up-regulated by TH within 4 -8 h and 13 are regulated by TH only in the brain. All cDNA fragments were sequenced and the identities of seven were determined through homology with known genes; an additional five TH-regulated genes were identified by hybridization with known cDNA clones. These include five transcription factors (including two members of the steroid receptor superfamily), a TH-converting deiodinase, two metabolic enzymes, a protein disulfide isomerase-like protein that may bind TH, a neural-specific cytoskeletal protein, and two hypophysiotropic neuropeptides. This is the first successful attempt to isolate a large number of TH-target genes in the developing vertebrate brain. The gene identities allow predictions about the gene regulatory networks underlying TH action on the brain, and the cloned cDNAs provide tools for understanding the basic molecular mechanisms underlying neural cell differentiation.

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Section: Identification Of T 3 -Regulated Neuralmentioning

confidence: 79%

Section: Identification Of T 3 -Regulated Neuralmentioning

confidence: 99%

Thyroid Hormone-dependent Gene Expression Program for Xenopus Neural Development

Denver

Pavgi

Shi

1997

Journal of Biological Chemistry

126

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“…The influence of TH on known target genes, namely RC3, MBP, MAP and PCP-2, has been demonstrated but has not increased our understanding of brain development (Silva & Rudas 1990, Farsetti et al 1991, Iniguez et al 1993, Zou et al 1994. Therefore, several attempts have been made to isolate hitherto unknown tri-iodothyronine (T 3 ) regulated genes during brain development by different modern techniques and other model systems (Muñoz et al 1991, Iglesias et al 1995, Vega-Nunez et al 1995, Denver et al 1997. Using Xenopus as an experimental model, where true T 3 negative conditions can be created, 34 cDNAs for TH-regulated genes in the diencephalon were identified.…”

Section: Introductionmentioning

confidence: 99%

Hypothyroidism alters mitochondrial morphology and induces release of apoptogenic proteins during rat cerebellar development

Singh

Upadhyay²,

Godbole

2003

Journal of Endocrinology

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Thyroid hormone (TH) deficiency leads to extensive apoptosis during cerebellar development, but the mechanism still remains unclear. Different signals also converge on mitochondria during apoptosis to induce the release of apoptogenic proteins that activate proteolytic cascade through specific enzymes called caspases. Here we studied the effect of hypothyroidism on alterations in mitochondrial structure and translocation of apoptogenic molecules during rat cerebellar development. Structural analysis of mitochondria was studied by electron microscopy. The translocation of apoptogenic molecules was analyzed by Western blotting. TH deficiency led to vacuolization, enlargement and decrease in the number of cristae. The majority of the proapoptotic molecule, Bax, was localized in mitochondria under hypothyroid conditions whereas a limited presence of Bax was detected in the euthyroid state. Translocation of cytochrome c, apoptosis-inducing factor (AIF) and second mitochondrial-derived activator of caspases (SMAC) from mitochondria to cytosol was detected primarily in early developmental stages in the hypothyroid condition. These experimental results demonstrate that TH maintains mitochondrial architecture and inhibits the release of apoptogenic molecules to prevent excess apoptosis during cerebellar development.

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“…However, relatively little is known about the functional role of T 3 in brain development because the information regarding the target genes is limited. Differential hybridization was performed to search for T 3 -regulated genes in vertebrates such as the frog and the rat (3,4,5,10,11,24,32,35), and the BTEB gene was identified as one of the most distinct T 3 -responsive genes in the Xenopus tadpole (3,4). The enhanced expression of the BTEB gene in response to T 3 has also been confirmed in the developing CNS of the rodent and was demonstrated to be a transcriptional event by a nuclear run-on assay (4).…”

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confidence: 98%

Functional Analysis of Basic Transcription Element Binding Protein by Gene Targeting Technology

Morita

Kobayashi

Yamashita

et al. 2003

Molecular and Cellular Biology

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Basic transcription element binding protein (BTEB) is a transcription factor with a characteristic zinc finger motif and is most remarkably enhanced by thyroid hormone T 3 treatment (R. J. Denver et al., J. Biol. Chem. 272:8179-8188, 1997). To investigate the function of BTEB per se and to touch on the effects of T 3 (3,5,3-triiodothyronine) on mouse development, we generated BTEB-deficient mice by gene knockout technology. Homologous BTEB؊/؊ mutant mice were bred according to apparently normal Mendelian genetics, matured normally, and were fertile. Mutant mice could survive for at least 2 years without evident pathological defects. From the expression of lacZ, which was inserted into the reading frame of the BTEB gene, BTEB showed a characteristic tissue-specific expression profile during the developmental process of brain and bone. Dramatically increased expression of BTEB was observed in Purkinje cells of the cerebellum and pyramidal cell layers of the hippocampus at P7 when synapses start to form in the brain. Although general behavioral activities such as locomotion, rearing, and speed of movement were not so much affected in the BTEB ؊/؊ mutant mice, they showed clearly reduced activity levels in rotorod and contextual fear-conditioning tests; this finding was probably due to defective functions of the cerebellum, hippocampus, and amygdala.

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Identification of the Mitochondrial NADH Dehydrogenase Subunit-3 as a Thyroid Hormone-Regulated Gene by Whole Genome PCR Analysis

Cited by 56 publications

References 0 publications

Thyroid Hormone-dependent Gene Expression Program for Xenopus Neural Development

Thyroid Hormone-dependent Gene Expression Program for Xenopus Neural Development

Hypothyroidism alters mitochondrial morphology and induces release of apoptogenic proteins during rat cerebellar development

Functional Analysis of Basic Transcription Element Binding Protein by Gene Targeting Technology

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