scholarly journals Rapid thyroid-hormone effect on mitochondrial and cytosolic ATP/ADP ratios in the intact liver cell

1985 ◽  
Vol 227 (1) ◽  
pp. 149-153 ◽  
Author(s):  
H J Seitz ◽  
M J Müller ◽  
S Soboll
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Adenine Nucleotide ◽  
Perfused Liver ◽  
Mitochondrial Matrix ◽  
Isolated Mitochondria ◽  
Hormone Effect ◽  
Adenine Nucleotide Transport ◽  
Atp Regeneration

The effect of thyroid-hormone application on cytosolic and mitochondrial ATP/ADP ratio was investigated in rat liver in vivo and in the isolated perfused organ. In vivo the ATP/ADP ratio in livers from hypothyroid rats was 0.84 +/- 0.08 in the mitochondrial matrix and 5.6 +/- 0.9 in the cytosol, as was observed in euthyroid controls. In contrast, hyperthyroidism was followed by a significant decrease in the mitochondrial and by an increase in the cytosolic ATP/ADP ratio (to 0.34 +/- 0.06 and 11.3 +/- 2.8 respectively). In the perfused liver from hypothyroid animals, addition of L-3,3',5-tri-iodothyronine in the perfusate also provoked, within 2 h, a significant decrease in the mitochondrial ATP/ADP ratio, whereas the cytosolic ratio was unaffected. From these and previous data in the isolated perfused liver and in isolated mitochondria from hypothyroid and tri-iodothyronine-treated rats it is concluded that thyroid hormones increase mitochondrial respiration and ATP regeneration, which is associated with an acceleration of mitochondrial adenine nucleotide transport and significant alterations in the mitochondrial and cytosolic ATP/ADP ratios.

Adenine nucleotide transport during cardiac ischemia

1981 ◽  
Vol 241 (5) ◽  
pp. H663-H671 ◽  
Author(s):  
K. F. LaNoue ◽  
J. A. Watts ◽  
C. D. Koch
Keyword(s):  
Adenine Nucleotide ◽  
Mitochondrial Protein ◽  
Heart Cells ◽  
Mitochondrial Matrix ◽  
Isolated Mitochondria ◽  
Palmitoyl Carnitine ◽  
Chain Acyl ◽  
Acyl Coenzyme A ◽  
Adenine Nucleotide Transport ◽  
Long Chain

The suggestion that long-chain acyl coenzyme A (CoA) derivatives may inhibit mitochondrial adenine nucleotide transport in heart cells during ischemia has been reevaluated. The effectiveness of media palmitoyl-CoA as an inhibitor is a function of mitochondrial protein and media adenine nucleotide concentrations. Extrapolation to the protein and adenine nucleotide levels of the cardiac cell suggest that physiological concentrations of cytosolic long-chain acyl-CoA would not inhibit adenosine 5'-triphosphate (ATP) transport. Palmitoyl-CoA was varied in the mitochondrial matrix by incubating the isolated mitochondria with and without palmitoyl carnitine. Intramitochondrial nucleotides were depleted by incubating the isolated mitochondria for various periods of time with arsenite and phosphate. Even at low substrate (matrix ATP) concentrations, no palmitoyl-CoA inhibition of ATP transport could be demonstrated. Further experiments showed that endogenous nucleotide levels are significantly depleted in mitochondria isolated from hearts made ischemic for 30-90 min. Since mitochondrial adenine nucleotide transport occurs by an exchange mechanism, this depletion of the internal pool of nucleotides from ischemic heart mitochondria may result in an irreversible diminution of ATP transport.

scholarly journals Endogenous thyroid hormones modulate pituitary somatotroph differentiation during chicken embryonic development

2004 ◽  
Vol 180 (1) ◽  
pp. 45-53 ◽  
Author(s):  
L Liu ◽  
TE Porter
Keyword(s):  
Thyroid Hormone ◽  
Embryonic Development ◽  
Thyroid Hormones ◽  
Synthesis Inhibitor ◽  
Hormone Synthesis ◽  
Thyroid Hormone Synthesis ◽  
Growth Hormone Cell ◽  
Thyroid Hormone Levels

Growth hormone cell differentiation normally occurs between day 14 and day 16 of chicken embryonic development. We reported previously that corticosterone (CORT) could induce somatotroph differentiation in vitro and in vivo and that thyroid hormones could act in combination with CORT to further augment the abundance of somatotrophs in vitro. The objective of the present study was to test our hypothesis that endogenous thyroid hormones regulate the abundance of somatotrophs during chicken embryonic development. Plasma samples were collected on embryonic day (e) 9-14. We found that plasma CORT and thyroid hormone levels increased progressively in mid-embryogenesis to e 13 or e 14, immediately before normal somatotroph differentiation. Administration of thyroxine (T4) and triiodothyronine (T3) into the albumen of fertile eggs on e 11 increased somatotroph proportions prematurely on e 13 in the developing chick embryos in vivo. Furthermore, administration of methimazole, the thyroid hormone synthesis inhibitor, on e 9 inhibited somatotroph differentiation in vivo, as assessed on e 14; this suppression was completely reversed by T3 replacement on e 11. Since we reported that T3 alone was ineffective in vitro, we interpret these findings to indicate that the effects of treatments in vivo were due to interactions with endogenous glucocorticoids. These results indicate that treatment with exogenous thyroid hormones can modulate somatotroph abundance and that endogenous thyroid hormone synthesis likely contributes to normal somatotroph differentiation.

scholarly journals Selective labelling and inactivation of creatine kinase isoenzymes by the thyroid hormone derivative N-bromoacetyl-3,3′,5-tri-iodo-l-thyronine

1993 ◽  
Vol 291 (2) ◽  
pp. 463-472 ◽  
Author(s):  
M Wyss ◽  
T Wallimann ◽  
J Köhrle
Keyword(s):  
Creatine Kinase ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Rat Heart ◽  
Covalent Modification ◽  
Regulation Of Transcription ◽  
Selective Labelling ◽  
Mitochondrial Fractions

Besides their well-known regulation of transcription by binding to nuclear receptors, thyroid hormones have been suggested to have direct effects on mitochondria. In a previous study, incubation of rat heart mitochondria with 125I-labelled N-bromoacetyl-3,3′,5-tri-iodo-L-thyronine (BrAcT3), a thyroid hormone derivative with an alkylating side chain, resulted in the selective labelling of a protein doublet around M(r) 45,000 on SDS/polyacrylamide gels [Rasmussen, Köhrle, Rokos and Hesch (1989) FEBS Lett. 255, 385-390]. Now, this protein doublet has been identified as mitochondrial creatine kinase (Mi-CK). Immunoblotting experiments with the cytoplasmic and mitochondrial fractions of rat heart, brain and liver, as well as inactivation studies with the purified chicken CK isoenzymes have further demonstrated that all four CK isoenzymes (Mia-, Mib-, M- and B-CK) are indeed selectively labelled by BrAcT3. However, in contrast with their bromoalkyl derivatives, thyroid hormones themselves did not compete for CK labelling, suggesting that not the thyroid hormone moiety but rather the bromoacetyl-driven alkylation of the highly reactive ‘essential’ thiol group of CK accounts for this selective labelling. Therefore the assumption that CK isoenzymes are thyroid-hormone-binding proteins has to be dismissed. Instead, bromoacetyl-based reagents may allow a very specific covalent modification and inactivation of CK isoenzymes in vitro and in vivo.

scholarly journals Thyroid Hormone Effect on Gene Expression of the Adenine Nucleotide Translocase in Different Rat Tissues

1988 ◽  
Vol 2 (11) ◽  
pp. 1127-1131 ◽  
Author(s):  
Wolfgang Höppner ◽  
Ulla B. Rasmussen ◽  
Ghaleb Abuerreish ◽  
Hartmut Wohlrab ◽  
Hans J. Seitz
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Adenine Nucleotide ◽  
Adenine Nucleotide Translocase ◽  
Rat Tissues ◽  
Hormone Effect

scholarly journals Thyroid Hormone Coordinates Respiratory Control Maturation and Adenine Nucleotide Translocator Expression in Heart In Vivo

Circulation ◽  
2000 ◽  
Vol 102 (11) ◽  
pp. 1323-1329 ◽  
Author(s):  
Michael A. Portman ◽  
Yun Xiao ◽  
Kun Qian ◽  
Russell L. Tucker ◽  
Steven M. Parish ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Adenine Nucleotide ◽  
Respiratory Control ◽  
Adenine Nucleotide Translocator

scholarly journals Thyroid hormones directly activate the expression of the human and mouse uncoupling protein-3 genes through a thyroid response element in the proximal promoter region

2005 ◽  
Vol 386 (3) ◽  
pp. 505-513 ◽  
Author(s):  
Gemma SOLANES ◽  
Neus PEDRAZA ◽  
Verónica CALVO ◽  
Antonio VIDAL-PUIG ◽  
Bradford B. LOWELL ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Uncoupling Protein ◽  
Gene Promoter ◽  
Proximal Promoter ◽  
Ucp3 Gene ◽  
Uncoupling Protein 3

The transcription of the human UCP3 (uncoupling protein-3) gene in skeletal muscle is tightly regulated by metabolic signals related to fatty acid availability. However, changes in thyroid status also modulate UCP3 gene expression, albeit by unknown mechanisms. We created transgenic mice bearing the entire human UCP3 gene to investigate the effect of thyroid hormones on human UCP3 gene expression. Treatment of human UCP3 transgenic mice with thyroid hormones induced the expression of the human gene in skeletal muscle. In addition, transient transfection experiments demonstrate that thyroid hormones activate the transcription of the human UCP3 gene promoter when MyoD and the TR (thyroid hormone receptor) were co-transfected. The action of thyroid hormones on UCP3 gene transcription is mediated by the binding of the TR to a proximal region in the UCP3 gene promoter that contains a direct repeat structure. An intact DNA sequence of this site is required for thyroid hormone responsiveness and TR binding. Chromatin immunoprecipitation assays revealed that the TR binds this element in vivo. The murine Ucp3 gene promoter was also dependent on MyoD and responsive to thyroid hormone in transient transfection assays. However, it was much less sensitive to thyroid hormone than the human UCP3 promoter. In summary, UCP3 gene transcription is activated by thyroid hormone treatment in vivo, and this activation is mediated by a TRE (thyroid hormone response element) in the proximal promoter region. Such regulation suggests a link between UCP3 gene expression and the effects of thyroid hormone on mitochondrial function in skeletal muscle.

scholarly journals How mitochondria produce reactive oxygen species

2008 ◽  
Vol 417 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Michael P. Murphy
Keyword(s):  
Reactive Oxygen Species ◽  
Oxidative Damage ◽  
Oxygen Species ◽  
Mitochondrial Matrix ◽  
Redox Signalling ◽  
Isolated Mitochondria ◽  
Mitochondrial Ros ◽  
Mammalian Mitochondria ◽  
O2 Production

The production of ROS (reactive oxygen species) by mammalian mitochondria is important because it underlies oxidative damage in many pathologies and contributes to retrograde redox signalling from the organelle to the cytosol and nucleus. Superoxide (O2•−) is the proximal mitochondrial ROS, and in the present review I outline the principles that govern O2•− production within the matrix of mammalian mitochondria. The flux of O2•− is related to the concentration of potential electron donors, the local concentration of O2 and the second-order rate constants for the reactions between them. Two modes of operation by isolated mitochondria result in significant O2•− production, predominantly from complex I: (i) when the mitochondria are not making ATP and consequently have a high Δp (protonmotive force) and a reduced CoQ (coenzyme Q) pool; and (ii) when there is a high NADH/NAD+ ratio in the mitochondrial matrix. For mitochondria that are actively making ATP, and consequently have a lower Δp and NADH/NAD+ ratio, the extent of O2•− production is far lower. The generation of O2•− within the mitochondrial matrix depends critically on Δp, the NADH/NAD+ and CoQH2/CoQ ratios and the local O2 concentration, which are all highly variable and difficult to measure in vivo. Consequently, it is not possible to estimate O2•− generation by mitochondria in vivo from O2•−-production rates by isolated mitochondria, and such extrapolations in the literature are misleading. Even so, the description outlined here facilitates the understanding of factors that favour mitochondrial ROS production. There is a clear need to develop better methods to measure mitochondrial O2•− and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling.

scholarly journals Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses

2016 ◽  
Vol 113 (24) ◽  
pp. E3451-E3460 ◽  
Author(s):  
Elvira Alonso-Merino ◽  
Rosa Martín Orozco ◽  
Lidia Ruíz-Llorente ◽  
Olaia A. Martínez-Iglesias ◽  
Juan Pedro Velasco-Martín ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Transcriptional Activation ◽  
Hormone Receptors ◽  
Target Genes ◽  
Direct Interaction ◽  
Beneficial Effects ◽  
Hormone Administration ◽  
Fibrotic Diseases

TGF-β, the most potent profibrogenic factor, acts by activating SMAD (mothers against decapentaplegic) transcription factors, which bind to SMAD-binding elements in target genes. Here, we show that the thyroid hormone triiodothyronine (T3), through binding to its nuclear receptors (TRs), is able to antagonize transcriptional activation by TGF-β/SMAD. This antagonism involves reduced phosphorylation of SMADs and a direct interaction of the receptors with SMAD3 and SMAD4 that is independent of T3-mediated transcriptional activity but requires residues in the receptor DNA binding domain. T3 reduces occupancy of SMAD-binding elements in response to TGF-β, reducing histone acetylation and inhibiting transcription. In agreement with this transcriptional cross-talk, T3 is able to antagonize fibrotic processes in vivo. Liver fibrosis induced by carbon tetrachloride is attenuated by thyroid hormone administration to mice, whereas aged TR knockout mice spontaneously accumulate collagen. Furthermore, skin fibrosis induced by bleomycin administration is also reduced by the thyroid hormones. These findings define an important function of the thyroid hormone receptors and suggest TR ligands could have beneficial effects to block the progression of fibrotic diseases.

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