scholarly journals FINE STRUCTURAL ALTERATIONS IN CELL PARTICLES DURING CHEMICAL CARCINOGENESIS

1961 ◽  
Vol 10 (1) ◽  
pp. 23-36 ◽  
Author(s):  
Joseph C. Arcos ◽  
Hans H. Gosch ◽  
David Zickafoose
Keyword(s):  
Azo Dye ◽  
Chemical Carcinogenesis ◽  
Liver Mitochondria ◽  
Mitochondrial Swelling ◽  
Rat Liver Mitochondria ◽  
Significant Modification ◽  
Liver Growth ◽  
Structural Alterations ◽  
Swelling Studies ◽  
Reversible Reduction

The previous studies on the correlation between tumor incidence and changes in microsomal and mitochondrial swelling during feeding of 3'-methyl-4-dimethylaminoazobenzene to rats have been extended to other hepatic carcinogens. Administration of 4'-fluoro-4-dimethylaminoazobenzene, 4'-ethyl-2-methyl-4-dimethylaminoazobenzene, 2-acetylam-inofluorene, ethionine, and tannic acid were found to produce drastic alterations of the swelling of rat liver mitochondria. In contrast to these compounds, feeding of the non-carcinogenic azobenzene and 4-diethylaminoazobenzene produced only small changes in swelling. Significant modification in the over-all pattern of the swelling curve was observed when the usual concentration of 3'-methyl-4-dimethylaminoazobenzene was reduced, but not when the riboflavin level in the diet was increased tenfold. Feeding of high levels of this dye to the guinea pig did not affect mitochondrial swelling which is consistent with the resistance of this species to azo-dye carcinogenesis. Hypophysectomy provides protection against the alterations, produced by feeding 3'-methyl-4-dimethylaminoazobenzene, in the characteristics of thyroxine- or mercuric chloride-induced mitochondrial swelling. Studies with citric cycle substrates on mitochondrial swelling suggest block of the glutamate ⇌ α-keto-glutarate pathway after feeding 3'-methyl-4-dimethylaminoazobenzene for 4 weeks. There is a considerable, but reversible, reduction of certain types of mitochondrial swelling in two situations associated with rapid liver growth: after partial hepatectomy and after intraperitoneal injection of 20-methylcholanthrene. Naphthacene, however, which also stimulates rapid liver growth, does not affect mitochondrial swelling.

Quantitation of effects on mitochondrial swelling: some effects of ATP and aging

1962 ◽  
Vol 17 (6) ◽  
pp. 979-984 ◽  
Author(s):  
Charles McGaughey
Keyword(s):  
Aging Time ◽  
Quantitative Measurement ◽  
Liver Mitochondria ◽  
Inhibitory Effect ◽  
Rate Of Change ◽  
Mitochondrial Swelling ◽  
Rat Liver Mitochondria ◽  
Logarithmic Function ◽  
Swelling Rate ◽  
Mitochondrial Volume

A method has been devised for the quantitative measurement of relative effects of substances or conditions on rate of change of mitochondrial volume. It can be used to study the effects progressively as the mitochondria swell. By this means, the effects of adenosine triphosphate (ATP) and aging on mitochondrial swelling were investigated. It was found that at constant mitochondrial volume, the rate of change of volume is a logarithmic function of aging time. The swelling of fresh mitochondria was mildly inhibited by ATP at very low volumes. Aging of rat liver mitochondria caused this inhibitory effect to be replaced by enhancement of swelling, which became greater in magnitude and was retained through larger volumes as aging time increased. The swelling enhancement was followed by inhibition, the magnitude of which increased with further swelling. The inhibitory effect of ATP on swelling of mouse liver mitochondria underwent a sudden marked increase at a particular mitochondrial volume independent of aging time and time of ATP exposure. At lower volumes the effect of ATP increased with aging time and swelling rate, whereas at larger volumes this relation ceased to be apparent. The possible significance of these results is discussed. Submitted on January 22, 1962

scholarly journals The transport of sulphate and sulphite in rat liver mitochondria

1974 ◽  
Vol 142 (1) ◽  
pp. 127-137 ◽  
Author(s):  
M. Crompton ◽  
F. Palmieri ◽  
Michela Capano ◽  
E. Quagliariello
Keyword(s):  
Rat Liver ◽  
Liver Mitochondria ◽  
Mitochondrial Swelling ◽  
Rat Liver Mitochondria ◽  
Additional Mechanism ◽  
Low Concentrations ◽  
Hydroxyl Ion ◽  
Osmotic Solution

1. The mechanism of sulphite and sulphate permeation into rat liver mitochondria was investigated. 2. Extramitochondrial sulphite and sulphate elicit efflux of intramitochondrial phosphate, malate, succinate and malonate. The sulphate-dependent effluxes and the sulphite-dependent efflux of dicarboxylate anions are inhibited by butylmalonate, phenylsuccinate and mersalyl. Inhibition of the phosphate efflux produced by sulphite is caused by mersalyl alone and by N-ethylmaleimide and butylmalonate when present together. 3. External sulphite and sulphate cause efflux of intramitochondrial sulphate, and this is inhibited by butylmalonate, phenylsuccinate and mersalyl. 4. External sulphite and sulphate do not cause efflux of oxoglutarate or citrate. 5. Mitochondria swell when suspended in an iso-osmotic solution of ammonium sulphite; this is not inhibited by N-ethylmaleimide or mersalyl. 6. Low concentrations of sulphite, but not sulphate, produce mitochondrial swelling in iso-osmotic solutions of ammonium malate, succinate, malonate, sulphate, or phosphate in the presence of N-ethylmaleimide. 7. It is concluded that both sulphite and sulphate may be transported by the dicarboxylate carrier of rat liver mitochondria and also that sulphite may permeate by an additional mechanism; the latter may involve the permeation of sulphurous acid or SO2 or an exchange of the sulphite anion for hydroxyl ion(s).

scholarly journals Liver mitochondrial pyrophosphate concentration is increased by Ca2+ and regulates the intramitochondrial volume and adenine nucleotide content

1987 ◽  
Vol 246 (3) ◽  
pp. 715-723 ◽  
Author(s):  
A M Davidson ◽  
A P Halestrap
Keyword(s):  
Adenine Nucleotide ◽  
Hormone Treatment ◽  
Liver Mitochondria ◽  
Mitochondrial Swelling ◽  
Rat Liver Mitochondria ◽  
Nucleotide Content ◽  
Mitochondrial Inner Membrane ◽  
Matrix Volume ◽  
The Matrix ◽  
K Permeability

1. The matrix pyrophosphate (PPi) content of isolated energized rat liver mitochondria incubated in the presence of ATP, Mg2+, Pi and respiratory substrate was about 100 pmol/mg of protein. 2. After incubation with sub-micromolar [Ca2+], this was increased by as much as 300%. There was a correlation between the effects of Ca2+ on PPi and on the increase in matrix volume reported previously [Halestrap, Quinlan, Whipps & Armston (1986) Biochem. J. 236, 779-787]. Half-maximal effects were seen at 0.3 microM-Ca2+. 3. Coincident with these effects, the total adenine nucleotide content increased in a carboxyatractyloside-sensitive manner. 4. Incubation with 0.2-0.5 mM-butyrate induced similar but smaller effects on mitochondrial swelling and matrix PPi and total adenine nucleotide content. Addition of butyrate after Ca2+, or vice versa, caused Ca2+-induced mitochondrial swelling to stop or reverse, while matrix PPi increased 30-fold. 5. Addition of atractyloside or the omission of ATP from incubations greatly enhanced swelling induced by Ca2+ without increasing matrix PPi. 6. Swelling of mitochondria incubated under de-energized conditions in iso-osmotic KSCN was progressively enhanced by the addition of increasing concentrations of PPi (1-20 mM) or valinomycin. 7. In iso-osmotic potassium pyrophosphate swelling was slow initially, but accelerated with time. This acceleration was inhibited by ADP, whereas carboxyatractyloside induced rapid swelling. Swelling in other iso-osmotic PPi salts showed that the rate of entry decreased in the order NH4+ greater than K+ greater than Na+ greater than Li+, whereas choline, tetramethylammonium and Tris did not enter. It is suggested that the adenine nucleotide translocase transports small univalent cations when PPi is bound and that PPi can also be transported when the transporter is in the conformation induced by carboxyatractyloside. 8. It is concluded that Ca2+ and butyrate cause swelling of energized mitochondria through this effect of PPi on K+ permeability of the mitochondrial inner membrane. 9. Freeze-clamped livers from rats treated with glucagon or phenylephrine show 30-50% increases in tissue PPi. It is proposed that Ca2+-mediated increases in mitochondrial PPi are responsible for the increase in matrix volume and total adenine nucleotide content observed after hormone treatment.

scholarly journals Structural changes in mitochondria induced by uncoupling reagents. The response to proteolytic enzymes

1968 ◽  
Vol 106 (3) ◽  
pp. 711-717 ◽  
Author(s):  
Eugene C. Weinbach ◽  
Joel Garbus
Keyword(s):  
Structural Changes ◽  
Proteolytic Enzymes ◽  
Free Acid ◽  
Liver Mitochondria ◽  
Mitochondrial Proteins ◽  
Rat Liver Mitochondria ◽  
Phospholipid Complex ◽  
Structural Alterations ◽  
Uncoupling Of Oxidative Phosphorylation ◽  
Contrast Interaction

Interaction of uncoupling reagents with bovine serum albumin markedly inhibited its hydrolysis by proteolytic enzymes. The inhibition presumably is due to conformational transitions in the protein substrate induced by the binding of the ligand–uncoupling reagents. The proteolysis of casein, a protein that does not bind these reagents, was not affected, indicating that the proteinases themselves were not inactivated. In contrast, interaction of uncoupling reagents with freshly isolated rat liver mitochondria enhanced their susceptibility to proteolytic enzymes. This was shown by an increase in the release of ninhydrin-reacting material, by an increase in free acid groups and by a decrease in the turbidity of the mitochondrial suspensions. These effects, although opposite in direction to those obtained with albumin, are also presumed to indicate structural changes in the mitochondrial proteins and a disorganization of the protein–phospholipid complex. It is suggested that such structural alterations are expressed functionally as the uncoupling of oxidative phosphorylation.

Ca(2+)-induced mitochondrial membrane permeabilization: role of coenzyme Q redox state

1995 ◽  
Vol 269 (1) ◽  
pp. C141-C147 ◽  
Author(s):  
A. J. Kowaltowski ◽  
R. F. Castilho ◽  
A. E. Vercesi
Keyword(s):  
Rat Liver ◽  
Coenzyme Q ◽  
Chain Complex ◽  
Liver Mitochondria ◽  
Ruthenium Red ◽  
Membrane Permeabilization ◽  
Mitochondrial Swelling ◽  
Rat Liver Mitochondria ◽  
Experimental Conditions ◽  
Protein Thiols

Rotenone-poisoned rat liver mitochondria energized by succinate addition, after a 5-min period of preincubation in presence of 10 microM Ca2+, produce H2O2 at much faster rates, undergo extensive swelling, and are not able to retain the membrane potential and accumulated Ca2+. Similar results were obtained when a suspension of rat liver mitochondria preincubated in anaerobic medium for 5 min was reoxygenated. The addition of either ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, ruthenium red, catalase, or dithiothreitol, just before succinate or O2 addition, prevented mitochondrial swelling, indicating the involvement of Ca2+, reactive oxygen species, and oxidation of membrane protein thiols in this process of membrane permeabilization. Inhibition of mitochondrial swelling by cyclosporin A suggests that the membrane alterations observed under these experimental conditions are related to opening of the permeability transition pore. The presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone, which prevents Ca2+ cycling across the membrane, did not inhibit mitochondrial swelling when Ca2+ influx into the mitochondrial matrix was driven by a high Ca2+ gradient. When rotenone plus antimycin A-poisoned mitochondria were energized by N,N,N',N'-tetramethyl-p-phenylenediamine, which reduces respiratory chain complex IV, mitochondrial swelling did not occur, unless succinate, which reduces coenzyme Q, was also added. It is concluded that reduced coenzyme Q is the electron source for oxygen radical production during Ca(2+)-stimulated oxidative damage of mitochondria.

Interaction of insulin and chromium (III) on mitochondrial swelling

1963 ◽  
Vol 204 (6) ◽  
pp. 1028-1030 ◽  
Author(s):  
William J. Campbell ◽  
Walter Mertz
Keyword(s):  
Rat Liver ◽  
Considerable Increase ◽  
Liver Mitochondria ◽  
Mitochondrial Swelling ◽  
Rat Liver Mitochondria

Swelling of rat liver mitochondria was significantly increased by 1.6 x 10–3 mm concentrations of insulin, but not with 1.6 x 10–4 mm insulin. 6 x 10–5 µmoles of chromium (III) per milliliter in the absence of insulin did not significantly increase swelling rates. Addition of insulin and chromium at concentrations which were ineffective by themselves, led to a considerable increase of mitochondrial swelling. On the basis of these and other data, it is proposed that trace amounts of chromium facilitate the tissue-insulin interaction by forming a complex with the intrachain disulfide of the hormone.

scholarly journals PREVENTION OF PHOSPHATE - INDUCED MITOCHONDRIAL SWELLING

1962 ◽  
Vol 15 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Arnold J. Kroll ◽  
Toichiro Kuwabara
Keyword(s):  
Electron Microscope ◽  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Bovine Serum ◽  
Liver Mitochondria ◽  
Mitochondrial Swelling ◽  
Rat Liver Mitochondria ◽  
Isolated Rat Liver ◽  
Isolated Rat

The prevention of phosphate-induced mitochondrial swelling in the whole retina of the rabbit was studied with the electron microscope. It was found that a mixture of ATP, Mg++, and bovine serum albumin protected the mitochondria in vitro. This finding confirmed the results obtained spectrophotometrically with isolated rat liver mitochondria by Lehninger.

scholarly journals Synthetic and natural polyanions induce cytochrome c release from mitochondria in vitro and in situ

2011 ◽  
Vol 300 (5) ◽  
pp. C1193-C1203 ◽  
Author(s):  
Boris F. Krasnikov ◽  
Nickolay S. Melik-Nubarov ◽  
Lubava D. Zorova ◽  
Alevtina E. Kuzminova ◽  
Nickolay K. Isaev ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Rat Liver ◽  
Mitochondrial Permeability Transition ◽  
Hydrophobic Interactions ◽  
Liver Mitochondria ◽  
Mitochondrial Swelling ◽  
Molar Ratio ◽  
Rat Liver Mitochondria ◽  
Cytochrome C Release

A synthetic polyanion composed of styrene, maleic anhydride, and methacrylic acid (molar ratio 56:37:7) significantly inhibited the respiration of isolated rat liver mitochondria in a time-dependent fashion that correlated with 1) collapse of the mitochondrial membrane potential and 2) high amplitude mitochondrial swelling. The process is apparently Ca2+ dependent. Since it is blocked by cyclosporin A, the process is ascribed to induction of the mitochondrial permeability transition. In mitoplasts, i.e., mitochondria lacking their outer membranes, the polyanion rapidly blocked respiration. After incubation of rat liver mitochondria with the polyanion, cytochrome c was released into the incubation medium. In solution, the polyanion modified by conjugation with fluorescein formed a complex with cytochrome c. Addition of the polyanion to cytochrome c-loaded phosphatidylcholine/cardiolipin liposomes induced the release of the protein from liposomal membrane evidently due to coordinated interplay of Coulomb and hydrophobic interactions of the polymer with cytochrome c. We conclude that binding of the polyanion to cytochrome c renders it inactive in the respiratory chain due to exclusion from its native binding sites. Apparently, the polyanion interacts with cytochrome c in mitochondria and releases it to the medium through breakage of the outer membrane as a result of severe swelling. Similar properties were demonstrated for the natural polyanion, tobacco mosaic virus RNA. An electron microscopy study confirmed that both polyanions caused mitochondrial swelling. Exposure of cerebellar astroglial cells in culture to the synthetic polyanion resulted in cell death, which was associated with nuclear fragmentation.

scholarly journals Fine Structural Alterations in Cell Particles During Chemical Carcinogenesis

1960 ◽  
Vol 7 (1) ◽  
pp. 49-60 ◽  
Author(s):  
Joseph C. Arcos ◽  
George W. Griffith ◽  
Richard W. Cunningham
Keyword(s):  
Ph Dependence ◽  
Chemical Carcinogenesis ◽  
Normal Liver ◽  
Liver Mitochondria ◽  
Unit Weight ◽  
Rat Liver Mitochondria ◽  
Swelling Properties ◽  
Carcinogenic Process ◽  
Sulfhydryl Compounds

Swelling under carefully controlled conditions has been used to study alterations in the structure of rat liver mitochondria as a result of feeding azo dyes. The changes of the swelling properties of the mitochondria during feeding of the hepatocarcinogenic 3'-methyl-4-dimethylaminoazobenzene are essentially comparable to those observed previously with the microsomes, under the same dietary conditions. These alterations in mitochondrial swelling are not related to changes in the amount of these cell particulates per unit weight of tissue, during feeding of this azo dye. As with the microsomes, feeding of the isomeric but relatively noncarcinogenic 2-methyl-4-dimethylaminoazobenzene does not affect swelling. The structural differences between liver and hepatoma mitochondria show up not only in the rate and extent of swelling but also in the form of the curves of pH dependence. The influence of ketones and sulfhydryl compounds on the swelling of normal liver mitochondria were studied, with particular emphasis to the role of sulfhydryl groups in membrane permeability. The sudden steep rise in the tumor incidence in groups of rats fed 3'-methyl-4-dimethylaminoazobenzene for increasing intervals of time occurs at about 4 weeks. This time correlates with the point of the minimum swelling of microsomes and mitochondria isolated from the livers of rats fed this same dye. Thus, a correlation is established between the alterations of the swelling properties of these particulates and the carcinogenic process.

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