ROLE OF PROTEIN SYNTHESIS IN COLD-INDUCED CHANGES IN PURINE NUCLEOTIDE BINDING AND POLYPEPTIDE COMPOSITION OF RAT BROWN ADIPOSE TISSUE (BAT) MITOCHONDRIA

Rapid increases in atractyloside-insensitive binding of purine nucleotides (ADP or GDP) and in a polypeptide of 32 000 occur in brown adipose tissue mitochondria of the rat during acclimation to cold. The increased binding is apparent within 1 h and reaches a maximum after 3–7 days of exposure to 4 °C. The increase in the 32 000 peptide occurs more slowly and reaches a maximum after 2–3 weeks. There is a simultaneous decrease in a polypeptide of 96 000, apparent after 1 day and reaching a maximum after 1–2 weeks. Results are interpreted in terms of the appearance of an increased amount of the purine nucleotide-sensitive proton conductance pathway in association with the development of an enhanced thermogenic capacity of brown adipose tissue mitochondria during acclimation of the rat to cold.

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Roles of noradrenaline and protein synthesis in the cold-induced increase in purine nucleotide binding by rat brown adipose tissue mitochondria

Canadian Journal of Biochemistry ◽

10.1139/o79-118 ◽

1979 ◽

Vol 57 (6) ◽

pp. 968-976 ◽

Cited By ~ 95

Author(s):

Michel Desautels ◽

Jean Himms-Hagen

Keyword(s):

Protein Synthesis ◽

Adipose Tissue ◽

Cold Stress ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Intravenous Infusion ◽

Nucleotide Binding ◽

Proton Conductance ◽

Purine Nucleotide ◽

Brown Adipose

Exposure of a rat to cold (4 °C) is known to induce a biphasic change in brown adipose tissue mitochondria, believed to reflect alterations in the thermogenic, purine nucleotide sensitive proton conductance pathway; an initial rapid and large increase in purine nucleotide binding, unaccompanied by any marked change in the 32 000 polypeptide which is the binding site for these nucleotides, is followed by a slower increase in concentration of the 32 000 polypeptide accompanied by a further increase in purine nucleotide binding. The initial rapid effect of cold stress was mimicked by intravenous infusion of noradrenaline; neither the effect of cold exposure for 24 h nor the effect of intravenous infusion of noradrenaline was prevented by cycloheximide. In contrast, the slow adaptive changes in the mitochondria did not occur in response to prolonged (2 weeks) treatment with noradrenaline, although such treatment did induce the expected tissue hypertrophy accompanied by mitochondrial proliferation. Cold-induced (1 week) increases in purine nucleotide binding and 32 000 polypeptide were not prevented by oxytetracycline. The increase in purine nucleotide binding during the 2nd day of cold exposure was prevented by cycloheximide. The effect of cycloheximide on the increase in the 32 000 polypeptide could not be assessed because sufficiently long-term experiments could not be done with this compound. Thus, the initial response to cold stress appears to involve unmasking of mitochondrial proton conductance pathway sites, most probably mediated by noradrenaline. The slower adaptive response occurs in parallel with tissue hypertrophy, which itself may be mediated by noradrenaline, and appears to require cytosolic but not mitochondrial protein synthesis. However, the changes in mitochondrial composition which result in an increased concentration of proton conductance pathway sites are not mediated by noradrenaline.

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EFFECTS OF DIET AND ACUTE NORADRENALINE TREATMENT ON BROWN ADIPOSE TISSUE DEVELOPMENT AND MITOCHONDRIAL PURINE-NUCLEOTIDE BINDING

Quarterly Journal of Experimental Physiology ◽

10.1113/expphysiol.1982.sp002634 ◽

1982 ◽

Vol 67 (2) ◽

pp. 259-268 ◽

Cited By ~ 45

Author(s):

Sarah L. Brooks ◽

Nancy J. Rothwell ◽

Michael J. Stock

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Nucleotide Binding ◽

Purine Nucleotide ◽

Tissue Development ◽

Brown Adipose ◽

Adipose Tissue Development

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Fatty acid utilization and purine nucleotide binding in brown adipose tissue of genetically obese (/) mice

Life Sciences ◽

10.1016/0024-3205(83)90101-7 ◽

1983 ◽

Vol 32 (18) ◽

pp. 2123-2130 ◽

Cited By ~ 10

Author(s):

Sylvette Bas ◽

Elisabeth Imesch ◽

Daniel Ricquier ◽

Françoise Assimacopoulos-Jeannet ◽

Josiane Seydoux ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Brown Adipose Tissue ◽

Nucleotide Binding ◽

Obese Mice ◽

Purine Nucleotide ◽

Fatty Acid Utilization ◽

Brown Adipose

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Role of thyroid hormone in cold-induced changes in rat brown adipose tissue mitochondria

Canadian Journal of Biochemistry ◽

10.1139/o82-065 ◽

1982 ◽

Vol 60 (5) ◽

pp. 530-537 ◽

Cited By ~ 58

Author(s):

Joan Triandafillou ◽

Cynthia Gwilliam ◽

Jean Himms-Hagen

Keyword(s):

Adipose Tissue ◽

Thyroid Hormone ◽

Brown Adipose Tissue ◽

Cytochrome Oxidase ◽

Polypeptide Composition ◽

Inner Mitochondrial Membrane ◽

Interscapular Brown Adipose Tissue ◽

Brown Adipose ◽

Intact Rats

The role of thyroid gland in cold-induced growth of brown adipose tissue and in cold-induced adaptive changes in brown adipose tissue mitochondria was investigated. Interscapular brown adipose tissue of thyroidectomized rats maintained at 28 °C was of normal size (protein, cytochrome oxidase content) and its mitochondria were normal, as judged from the level of GDP binding and the polypeptide composition. (GDP binds to a 32 000 dalton polypeptide component of the inner mitochondrial membrane. This component is part of the thermogenic proton conductance pathway. The level of GDP binding is a sensitive indicator of the thermogenic state of the tissue.) Brown adipose tissue mitochondria of thyroidectomized rats exposed to 4 °C for 15 h did not show the usual increase in GDP binding, an indication of a lack of a thermogenic response; the response was restored in thyroxine-treated thyroidectomized animals. In thyroidectomized rats treated with a low maintenance dose of thyroxine (25 μg/kg, s.c., three times per week) and acclimated to cold (4 °C) for 2 weeks, a normal growth of brown adipose (increase in protein and cytochrome oxidase) and normal changes in mitochondria (increase in GDP binding and an increase in the proportion of polypeptides of molecular weight 31 200 – 34 400) occurred. Treatment of intact rats with a large dose of thyroxine (1000 μg/kg, s. c., per day) resulted in a large increase in wet weight, mainly due to lipid accumulation since only small increases in protein and cytochrome oxidase and no change in DNA content occurred; mitochondrial GDP binding was decreased and polypeptide composition unchanged. It is concluded that thyroid hormone exerts a permissive effect on the cold-induced, noradrenaline-mediated, unmasking of GDP-binding sites in brown adipose tissue. The failure of the thyroidectomized rat to survive at 4 °C is probably primarily due to its inability to activate thermogenesis in its brown adipose tissue. Thyroid hormone does not appear to be involved, other than in a permissive way, in long-term cold-induced growth and mitochondrial changes in brown adipose tissue, since these occur normally in the presence of only small amounts of thyroxine in thyroidectomized rats and do not occur in intact rats treated with large amounts of thyroxine.

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Hemin inhibits protein synthesis and degradation in isolated brown adipose tissue mitochondria

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y94-135 ◽

1994 ◽

Vol 72 (9) ◽

pp. 970-978 ◽

Cited By ~ 1

Author(s):

M. Desautels ◽

R. A. Dulos

Keyword(s):

Protein Synthesis ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Protoporphyrin Ix ◽

Significant Inhibition ◽

Aminolevulinate Synthase ◽

Bat Mitochondria ◽

Brown Adipose ◽

Protein Synthesis And Degradation ◽

Synthesis And Degradation

The primary objectives of this work were to evaluate the effects of hemin on protein synthesis and degradation in isolated brown adipose tissue (BAT) mitochondria. Exposure of mice to a cold environment (4 °C) caused a significant increase in 5′-aminolevulinate synthase (ALV synthase) activity in BAT coincident with an increase in the tissue mitochondrial protein content. Hemin caused significant inhibition of protein synthesis and of ATP-stimulated proteolysis in isolated BAT mitochondria. These effects were specific, as protoporphyrin IX, a precursor of heme, increased protein synthesis and had no effect on ATP-stimulated degradation of mitochondrial translation products. The end products of degradation of proteins synthesized within isolated mitochondria were amino acids released to the outside of the organelles. Hemin appeared to inhibit an early step of the degradation pathway, as it caused a significant reduction in labelled methionine release from the organelles but no accumulation of peptides. Hemin caused significant inhibition of ATP-stimulated hydrolysis of labelled casein by soluble mitochondrial fractions, while addition of protoporphyrin IX was much less effective. In contrast, protease activity associated with mitochondrial membranes was almost equally sensitive to inhibition by hemin and protoporphyrin IX. These results suggest that heme may play a role in BAT mitochondriogenesis by its action on protein synthesis and degradation within the organelles.Key words: thermoregulation, body weight, heme, 5′-aminolevulinate synthase, ATP-dependent proteolysis, protease, protoporphyrin IX.

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Effect of mazindol, d-amphetamine and diethylpropion on purine nucleotide binding to brown adipose tissue

Pharmacology Biochemistry and Behavior ◽

10.1016/0091-3057(86)90378-3 ◽

1986 ◽

Vol 25 (4) ◽

pp. 733-738 ◽

Cited By ~ 12

Author(s):

J.R. Lupien ◽

G.A. Bray

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Nucleotide Binding ◽

Purine Nucleotide ◽

Brown Adipose

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Hamster Brown-Adipose-Tissue Mitochondria. Purine Nucleotide Control of the Ion Conductance of the Inner Membrane, the Nature of the Nucleotide Binding Site

European Journal of Biochemistry ◽

10.1111/j.1432-1033.1976.tb10151.x ◽

1976 ◽

Vol 62 (2) ◽

pp. 223-228 ◽

Cited By ~ 201

Author(s):

David G. NICHOLLS

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Binding Site ◽

Nucleotide Binding ◽

Nucleotide Binding Site ◽

Purine Nucleotide ◽

Inner Membrane ◽

Ion Conductance ◽

Brown Adipose

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Role of prolactin in lactation-induced changes in brown adipose tissue

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.258.1.r51 ◽

1990 ◽

Vol 258 (1) ◽

pp. R51-R56 ◽

Cited By ~ 6

Author(s):

E. Chan ◽

R. Swaminathan

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Uncoupling Protein ◽

Energy Utilization ◽

Serum Prolactin ◽

Enzyme Linked Immunosorbent Assay ◽

Simultaneous Administration ◽

Brown Adipose ◽

Induced Changes

During lactation the efficiency of energy utilization is increased and brown adipose tissue (BAT) thermogenesis is suppressed. We have examined the role of prolactin in the suppression of BAT during lactation in the rat. Changes in BAT were studied using an enzyme-linked immunosorbent assay for the uncoupling protein (UCP). In the first experiment BAT from pregnant and lactating rats was examined at various times. Total UPC content of BAT decreased from 364 +/- 34 to 32 +/- 9 micrograms during late lactation (20 days). Serum prolactin (PRL) concentration was elevated during lactation and was highest at 10 days. When endogenous PRL was stimulated by injection of metoclopramide (1.67 mg/kg) for 5 days, UCP content of BAT decreased by 50%. This action of metoclopramide could be blocked by simultaneous administration of bromocriptine, an inhibitor of PRL secretion. Serum PRL concentration was elevated during metoclopramide administration but not when metoclopramide and bromocriptine were given together. We conclude that PRL is a possible mediator of the suppression of BAT during lactation.

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