Pyruvate oxidation in thyroid tissue

Dumont, Jacques Emile

doi:10.1016/0006-3002(62)90586-3

Cited by 12 publications

(4 citation statements)

References 14 publications

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“…total oxygen consumption (34). This is consornant with the observation that the QO2 of thyroid slices is well-maintained although no substrate is added to the medium (35)(36)(37). The endogenous substrate whose oxidation accounts for most of the oxygen consumed is, however, unknown.…”

Section: Discussionmentioning

confidence: 80%

Effects of Inorganic Iodide on the Intermediary Carbohydrate Metabolism of Surviving Sheep Thyroid Slices*

Green¹,

Ingbar²

1963

J. Clin. Invest.

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The rate of hormone formation by the thyroid in vivo is greatly influenced by acute alterations in the concentration of inorganic iodide in the extracellular fluid. In the rat (1-3) and in man (4,5), increasing concentrations of iodide in the plasma are associated with increased thyroidal uptake of iodine until a critical concentration of iodide is reached. Beyond this range, the formation of hormone declines. A similar relationship between extracellular iodide concentration and organic iodinations occurs in vitro in slices of sheep thyroid (6), whole lobes of rat thyroid (7), and homogenates of rat salivary gland (8). This relative inhibition of thyroid hormone formation induced by high concentrations of iodide is often termed the Wolff-Chaikoff phenomenon, and has never been fully explained. In normal animals, such inhibition is transient (9). Rarely, however, prolonged treatment with iodine does cause goiter and myxedema in man (10), possibly because the inhibitory effect of iodide persists.Recently, evidence has accumulated that the formation of hormone and oxidative metabolism in the thyroid are closely linked. First, the iodideconcentrating mechanism is dependent on phosphate bond energy (11, 12), and second, organic binding of thyroidal iodide appears to depend on electron transfers leading to generation of hydrogen peroxide (13-16). The present studies were designed to determine whether changes in the rate of hormone formation induced by varying the availability of iodide to thyroid slices in vitro are associated with, or can be ascribed to, alterations of intermediary metabolism within the thyroid. A preliminary report of these studies has appeared (17). METHODSPreparation of slices. Thyroid glands were obtained from freshly killed sheep and were brought from the abattoir to the laboratory packed in ice. A single gland was used in each experiment. Slices were cut with a Stadie-Riggs microtome, washed twice in ice-cold physiological saline solution, weighed on a torsion balance, and placed in Warburg vessels containing 2 or 3 ml of icecold medium. Tissue weights were quite uniform within individual experiments, but varied between approximately 50 and 300 mg per flask in different experiments.Preparation of media. The standard medium employed in control vessels was Krebs-Ringer-phosphate buffer (KRP), pH 7.4, with one-third the recommended concentration of CaClJ1 (18). Each milliliter of medium contained 1.5 or 2.0 mg of stable glucose, labeled with 0.5 to 1.5 /uc of C14.2 Vessels were incubated at 380 C under 100% oxygen in a Warburg apparatus for from 60 to 200 minutes. CO2 was absorbed by 0.2 ml of 10% KOH in a sidearm.Media containing desired concentrations of iodide were prepared by isosmotic substitution of NaI for NaCl in KRP. Several factors, however, might cause the ultimate concentration of iodide in the medium to deviate from that produced by the addition of NaI.

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Section: Discussionmentioning

confidence: 80%

Effects of Inorganic Iodide on the Intermediary Carbohydrate Metabolism of Surviving Sheep Thyroid Slices*

Green¹,

Ingbar²

1963

J. Clin. Invest.

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“…In thyroid tissues, the LDHA and LDHB expression levels were similar in follicular, oncocytic tumors and normal tissues (Figure 1B). The correlation between protein and mRNA levels for LDHA and LDHB was less relevant, but related to previous studies on cell metabolism where a mix between aerobic and anaerobic glycolysis was described in normal and tumor cells [21]–[22] (Figure S1). …”

Section: Resultsmentioning

confidence: 79%

Estrogen-Related Receptor Alpha Modulates Lactate Dehydrogenase Activity in Thyroid Tumors

et al. 2013

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Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor α (ERRα), a major factor of metabolic adaptation, is closely related to the oxidative metabolism and the proliferative status of the cells. To elucidate the role played by ERRα in the glycolytic adaptation of tumor cells, we focused on the regulation of lactate dehydrogenases A and B (LDHA, LDHB) and the LDHA/LDHB ratio. Our study included tissue samples from 10 classical and 10 oncocytic variants of follicular thyroid tumors and 10 normal thyroid tissues, as well as samples from three human thyroid tumor cell lines: FTC-133, XTC.UC1 and RO82W-1. We identified multiple cis-acting promoter elements for ERRα, in both the LDHA and LDHB genes. The interaction between ERRα and LDH promoters was confirmed by chromatin immunoprecipitation assays and in vitro analysis for LDHB. Using knock-in and knock-out cellular models, we found an inverse correlation between ERRα expression and LDH activity. This suggests that thyroid tumor cells may reprogram their metabolic pathways through the up-regulation of ERRα by a process distinct from that proposed by the recently revisited Warburg hypothesis.

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“…A possible explanation is suggested by the work of Chappell & Greville (1961), who showed that in 2,4-dinitrophenol-treated mitochondria oxidations that were dependent on the conversion of a-oxoglutarate into succinate remained rate-limited by the availability of ADP if oligomycin was also present. In thyroid-slice preparations the respiration is due to citric acidcycle activity, including this oxidation step (Dumont, 1962).…”

Section: Resultsmentioning

confidence: 99%

“…The methods used in the preparation and for the incubation of sheep thyroid slices were as described by Dumont (1964). The slices were incubated in a Warburg apparatus or in a Dubnoff metabolic incubator under an atmosphere of air or oxygen at 37°.…”

Section: Methodsmentioning

confidence: 99%

Influence of mitochondrial inhibitors on the respiration and energy-dependent uptake of iodide by thyroid slices

Tyler¹,

Gonze²,

Lamy³

et al. 1968

Biochemical Journal

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The influence of mitochondrial inhibitors, including oligomycin, antimycin and rotenone, on the iodide and oxygen uptake and the nucleotide content of incubated sheep thyroid slices was investigated. Each inhibitor strongly suppressed both iodide and oxygen uptake, and decreased the nucleoside triphosphate content of the slices. In most cases the addition of glucose or mitochondrial substrates restored iodide uptake in inhibitor-treated slices. Inhibitor concentrations sufficient to inhibit iodide uptake strongly had only slight effects on the thyroidal Na(+)+K(+)-activated adenosine triphosphatase. It is concluded that the inhibitors produce their effects by the inhibition in vivo of mitochondrial oxidative phosphorylation. ATP synthesis appears to be essential for iodide uptake to occur, and the high-energy intermediates (or energized state) of oxidative phosphorylation cannot be used to energize the uptake process. To a limited extent glycolytic ATP synthesis can support iodide uptake, which is therefore not exclusively dependent on aerobic metabolism. The mechanism of energy-linked iodide uptake is discussed.

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Pyruvate oxidation in thyroid tissue

Cited by 12 publications

References 14 publications

Effects of Inorganic Iodide on the Intermediary Carbohydrate Metabolism of Surviving Sheep Thyroid Slices*

Effects of Inorganic Iodide on the Intermediary Carbohydrate Metabolism of Surviving Sheep Thyroid Slices*

Estrogen-Related Receptor Alpha Modulates Lactate Dehydrogenase Activity in Thyroid Tumors

Influence of mitochondrial inhibitors on the respiration and energy-dependent uptake of iodide by thyroid slices

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