scholarly journals Influence of starvation and clofibrate administration on oxidative phosphorylation by rat liver mitochondria

1980 ◽  
Vol 190 (1) ◽  
pp. 191-198 ◽  
Author(s):  
B K A Rasheed ◽  
S Chhabra ◽  
C K R Kurup
Keyword(s):  
Cytochrome C ◽  
Binding Sites ◽  
Liver Mitochondria ◽  
Potassium Ferricyanide ◽  
Rat Liver Mitochondria ◽  
Albino Rats ◽  
Succinate Dehydrogenase Activity ◽  
Whole Cells ◽  
High Affinity

Whole cells, homogenates and mitochondrial obtained from the livers of albino rats which were starved for 6 days or more showed a 50% decrease in oxidative activity. The decrease could be corrected by the addition of cytochrome c in vitro. The phosphorylative activity of mitochondria remained unaffected. The decrease in oxidative rate was not observed when starving animals were given the anti-hypercholesterolaemic drug clofibrate. The total cellular concentration of cytochrome c was not affected by starvation. However, the concentration of the pigment in hepatic mitochondria isolated from starving animals was less than half that in normal mitochondria. Clofibrate-treated animals did not show a decreased concentration of cytochrome c in hepatic mitochondria. Mitochondria isolated from starving animals, though deficient in cytochrome c, did not show any decrease in succinate dehydrogenase activity or in the rate of substrate-dependent reduction of potassium ferricyanide or attendant phosphorylation. In coupled mitochondria, ferricyanide may not accept electrons from the cytochrome c in the respiratory chain. Starvation decreases the concentration of high-affinity binding sites for cytochrome c on the mitochondrial membrane. The dissociation constant increases in magnitude.

THE INHIBITION OF OXIDATIVE AND PHOSPHORYLATIVE ENZYMES IN RAT LIVER MITOCHONDRIA BY AMINOAZOBENZENE DERIVATIVES

1960 ◽  
Vol 38 (1) ◽  
pp. 1-11 ◽  
Author(s):  
W. C. McMurray
Keyword(s):  
Cytochrome C ◽  
Rat Liver ◽  
Pyridine Nucleotide ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Succinate Oxidation ◽  
Metabolic Block ◽  
Liver Carcinogen ◽  
Mitochondrial Dehydrogenase Activity

The liver carcinogen, dimethylaminoazobenzene, inhibited in vitro the oxidation of a variety of pyridine nucleotide linked substrates of rat liver mitochondria without affecting the process of oxidative phosphorylation. Cytochrome c oxidase activity was not inhibited by the carcinogen, nor was the succinoxidase activity, but the phosphorylation accompanying succinate oxidation was uncoupled. Similar effects were noted with other aminoazobenzene derivatives, but did not appear to be correlated with the ability of the compounds to evoke tumors.The site of the respiratory inhibition by dimethylaminoazobenzene appears to be at the level between reduced pyridine nucleotide and cytochrome c in the respiratory chain. Mitochondrial dehydrogenase activity was not inhibited, while the oxidation of reduced diphosphopyridine nucleotide was markedly decreased. The reduction of the electron acceptor, ferricyanide, by pyridine nucleotide linked substrates was also strongly inhibited but the reduction of tetrazolium compounds was not affected. The latter observations suggest that dimethylaminoazobenzene produces a metabolic block between reduced flavin and cytochrome c in the mitochondrial electron transport system.

Palladacycles catalyse the oxidation of critical thiols of the mitochondrial membrane proteins and lead to mitochondrial permeabilization and cytochrome c release associated with apoptosis

2008 ◽  
Vol 417 (1) ◽  
pp. 247-256 ◽  
Author(s):  
Débora P. Santana ◽  
Priscila A. Faria ◽  
Edgar J. Paredes-Gamero ◽  
Antonio C. F. Caires ◽  
Iseli L. Nantes ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Cytochrome C ◽  
Disulfide Bonds ◽  
Mitochondrial Membrane ◽  
Apoptotic Cell ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Cytochrome C Release ◽  
Mitochondrial Permeabilization

Permeabilization of the mitochondrial membrane has been extensively associated with necrotic and apoptotic cell death. Similarly to what had been previously observed for B16F10-Nex2 murine melanoma cells, PdC (palladacycle compounds) obtained from the reaction of dmpa (N,N-dimethyl-1-phenethylamine) with the dppe [1,2-ethanebis(diphenylphosphine)] were able to induce apoptosis in HTC (hepatoma, tissue culture) cells, presenting anticancer activity in vitro. To elucidate cell site-specific actions of dmpa:dppe that could respond to the induction of apoptosis in cancer cells in the present study, we investigated the effects of PdC on isolated RLM (rat liver mitochondria). Our results showed that these palladacycles are able to induce a Ca2+-independent mitochondrial swelling that was not inhibited by ADP, Mg2+ and antioxidants. However, the PdC-induced mitochondrial permeabilization was partially prevented by pre-incubation with CsA (cyclosporin A), NEM (N-ethylmaleimide) and bongkreic acid and totally prevented by DTT (dithiothreitol). A decrease in the content of reduced thiol groups of the mitochondrial membrane proteins was also observed, as well as the presence of membrane protein aggregates in SDS/PAGE without lipid and GSH oxidation. FTIR (Fourier-transform IR) analysis of PdC-treated RLM demonstrated the formation of disulfide bonds between critical thiols in mitochondrial membrane proteins. Associated with the mitochondrial permeabilization, PdC also induced the release of cytochrome c, which is sensitive to inhibition by DTT. Besides the contribution to clarify the pro-apoptotic mechanism of PdC, this study shows that the catalysis of specific protein thiol cross-linkage is enough to induce mitochondrial permeabilization and cytochrome c release.

Cytochrome c methylation

1989 ◽  
Vol 67 (9) ◽  
pp. 602-611 ◽  
Author(s):  
Woon Ki Pair ◽  
Young-Bong Cho ◽  
Blaise Frost ◽  
Sangduk Kim
Keyword(s):  
Cytochrome C ◽  
Liver Mitochondria ◽  
In Vitro Translation ◽  
Rat Liver Mitochondria ◽  
General Terms ◽  
Apocytochrome C ◽  
Enzymatic Methylation ◽  
Stokes Radius

In this review, protein methylation is outlined in general terms, highlighting the major amino acids that are methylated and some of the proteins in which they are found. The majority of the review examines the methylation of cytochrome c at Lys-77 of lower eukaryotes as a possible model for methylation studies. Early work involving the purification and characterization of the methyltransferase responsible for this methylation indicated cytochrome c was methylated posttranslationally, yet prior to import into the mitochondria. Methylation in vitro occurred only at the in vivo methylation site and only on cytochrome c. Later studies using in vitro translated apocytochrome c revealed that methylated, as compared with unmethylated, apocytochrome c was imported preferentially into yeast, but not rat liver, mitochondria. Efforts to discover the reasons for this preference have shown that methylation of apocytochrome c dramatically lowers its isoelectric point (against a predicted increase) and decrease its Stokes radius. A possible mechanism for these differences involving the disruption of hydrogen bonds is presented here with space-filling models. Finally, the in vivo significance of this modification is also discussed.Key words: yeast iso-1-apocytochrome c, enzymatic methylation, in vitro translation, protein methylase III, pI change.

scholarly journals Growth inhibitory action of saccharin and cyclamate on rats receiving a poor rice diet

1969 ◽  
Vol 23 (3) ◽  
pp. 505-509 ◽  
Author(s):  
M. I. Sabri ◽  
S. K. Sharma ◽  
C. R. Krishna Murti
Keyword(s):  
Inhibitory Action ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Succinate Dehydrogenase Activity ◽  
Deficient Diet ◽  
Balanced Diet ◽  
The Poor ◽  
Growth Inhibitory ◽  
Rice Diet

1. The effect of saccharin and cyclamate on growth of young rats fed on a poor rice diet or a balanced diet was investigated.2. Saccharin and cyclamate retarded the growth of rats on the multi-deficient diet but not of those on the well-balanced diet during an 8-week feeding period.3. The sweeteners did not produce any macroscopic or microscopic changes in the liver, kidneys, intestines, spleen or lungs of the animals receiving the poor rice diet other than the changes resulting from the nutritional deficiency of the diet.4. The sweeteners did not inhibit the liver xanthine oxidase activity of rats receiving the poor rice diet to an extent greater than the inhibition brought about by the deficiency of protein in the diet.5. When given by intubation to healthy rats, the sweeteners inhibited the induction of liver tryptophan oxygenase; given in vitro, they inhibited the succinate dehydrogenase activity of rat liver mitochondria.

THE INHIBITION OF OXIDATIVE AND PHOSPHORYLATIVE ENZYMES IN RAT LIVER MITOCHONDRIA BY AMINOAZOBENZENE DERIVATIVES

1960 ◽  
Vol 38 (1) ◽  
pp. 1-11
Author(s):  
W. C. McMurray
Keyword(s):  
Cytochrome C ◽  
Rat Liver ◽  
Pyridine Nucleotide ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Succinate Oxidation ◽  
Metabolic Block ◽  
Liver Carcinogen ◽  
Mitochondrial Dehydrogenase Activity

The liver carcinogen, dimethylaminoazobenzene, inhibited in vitro the oxidation of a variety of pyridine nucleotide linked substrates of rat liver mitochondria without affecting the process of oxidative phosphorylation. Cytochrome c oxidase activity was not inhibited by the carcinogen, nor was the succinoxidase activity, but the phosphorylation accompanying succinate oxidation was uncoupled. Similar effects were noted with other aminoazobenzene derivatives, but did not appear to be correlated with the ability of the compounds to evoke tumors.The site of the respiratory inhibition by dimethylaminoazobenzene appears to be at the level between reduced pyridine nucleotide and cytochrome c in the respiratory chain. Mitochondrial dehydrogenase activity was not inhibited, while the oxidation of reduced diphosphopyridine nucleotide was markedly decreased. The reduction of the electron acceptor, ferricyanide, by pyridine nucleotide linked substrates was also strongly inhibited but the reduction of tetrazolium compounds was not affected. The latter observations suggest that dimethylaminoazobenzene produces a metabolic block between reduced flavin and cytochrome c in the mitochondrial electron transport system.

scholarly journals The effects of diphenyleneiodonium on mitochondrial reactions. Relation of binding of diphenylene[125I]iodonium to mitochondria to the extent of inhibition of oxygen uptake

1976 ◽  
Vol 158 (2) ◽  
pp. 307-315 ◽  
Author(s):  
S J Gatley ◽  
H S A Sherratt
Keyword(s):  
Rat Liver ◽  
Binding Sites ◽  
Nadh Dehydrogenase ◽  
Liver Mitochondria ◽  
Nadh Oxidation ◽  
Affinity Constant ◽  
Rat Liver Mitochondria ◽  
High Affinity ◽  
Limiting Stage ◽  
Rate Limiting

1. Several ring-substituted derivatives of diphenyleneiodonium catalyse the exchange of Cl- and OH- ions across the inner membrane of rat liver mitochondria. They also inhibit state 3 and state 3u oxidations of glutamate plus malate in the presence of Cl- more than in its absence. Most have activities similar to diphenyleneiodonium, although 2,4-dichlorodiphenyleneiodonium is up to 50 times more active. 2. Diphenyleneiodonium inhibits soluble rat liver NADH dehydrogenase and NADH oxidation by rat liver sub-mitochondrial particles directly; 2,4-dichlorodiphenyleneiodonium is only about twice as inhibitory. 3. Liver mitochondria contain two classes of binding sites for diphenylene[125I]iodonium, namely high-affinity sites with an affinity constant of 3 X 10(5) M-1 (1–2 nmol/mg of protein), and low-affinity sites with an affinity constant of 1.3 X 10(3) M-1 (80 nmol/mg of protein). Both sites occur in hepatocytes with a relative enrichment of the low-affinity site. Nadh dehydrogenase preparations only apparently contain high-affinity binding sites. Only low-affinity sites occur in erythrocytes. 4. 2,4-Dichlorodiphenyleneiodonium competes with diphenylene[125I]iodonium for both low- and high-affinity sites, whereas tri-n-propyltin only competes for the low-affinity sites. 5. The high-affinity sites are apparently associated with NADH dehydrogenase and the low-affinity sites probably represent electrostatic binding of diphenylene[125I]iodonium to phospholipids. The high-affinity site does not appear to be associated with a rate-limiting stage of NADH oxidation.

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.

Thyroid hormone and not growth hormone is the principle regulator of mammalian mitochondrial biogenesis

1989 ◽  
Vol 121 (2) ◽  
pp. 223-228 ◽  
Author(s):  
A. Mutvei ◽  
B. Husman ◽  
G. Andersson ◽  
B. D. Nelson
Keyword(s):  
Growth Hormone ◽  
Thyroid Hormone ◽  
Mitochondrial Biogenesis ◽  
Binding Sites ◽  
Specific Binding ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Mitochondrial Membranes

Abstract. T3 and GH have been implicated in the regulation of mitochondrial biogenesis. Since thyroid hormone promotes the synthesis of growth hormone, its control of human mitochondrial biogenesis could arise through a permissive action on GH biosynthesis. This was studied in hypophysectomized rats treated with T3 and/or human GH by the continuous infusion of hormone for 6 days from mini-infusion pumps implanted sc. Increases in mitochondrial respiration, enzyme activites, and protein synthesis were found in isolated liver mitochondria from rats receiving T3. In contrast, GH alone had no effect, nor did it increase the response to T3. Since it has been argued that mitochondrial biogenesis results from a direct interaction (binding) of GH with mitochondria, GH-specific binding sites were measured with 125I-bGH, a specific somatogenic receptor ligand, in isolated mitochondrial membranes in vitro. In addition, the intracellular endocytic uptake of 125I-bGH injected in vivo was compared in purified subcellular membrane fractions and mitochondria. No evidence in favour of specific GH interaction on mitochondrial membranes was found by either test. It is concluded that T3 exerts a direct, rather than permissive, effect on mitochondrial biogenesis, and that high affinity binding sites for GH are not present in rat liver mitochondria.

Magnetic nanostructured lipid carrier for dual triggered curcumin delivery: Preparation, characterization and toxicity evaluation on isolated rat liver mitochondria

2021 ◽  
pp. 088532822110346
Author(s):  
Mohammad Yoozbashi ◽  
Hamid Rashidzadeh ◽  
Mehraneh Kermanian ◽  
Somayeh Sadighian ◽  
Mir-Jamal Hosseini ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Nanostructured Lipid Carrier ◽  
Mitochondrial Toxicity ◽  
X Ray Diffraction ◽  
Temperature Dependent ◽  
Reducing Ability ◽  
Transmission Electron

In this research, magnetic nanostructured lipid carriers (Mag-NLCs) were synthesized for curcumin (CUR) delivery. NLCs are drug-delivery systems prepared by mixing solid and liquid (oil) lipids. For preparation of NLCs, cetylpalmitate was selected as solid lipid and fish oil as liquid lipid. CUR-Mag-NLCs were prepared using high-pressure homogenization technique and were characterized by methods including X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), and dynamic light scattering (DLS). The CUR-Mag-NLCs were developed as a particle with a size of 140 ± 3.6 nm, a polydispersity index of 0.196, and a zeta potential of −22.6 mV. VSM analysis showed that the CUR-Mag-NLCs have excellent magnetic properties. Release rate of the drug was higher at 42 °C than 37 °C, indicating that release of the synthesized nanoparticles is temperature-dependent. Evaluation of mitochondrial toxicity was done using the isolated rats liver mitochondria including glutathione (GSH), malondialdehyde (MDA), and the ferric- reducing ability of plasma (FRAP) assays to study biosafety of the CUR-Mag-NLCs. Results of In vitro study on the isolated mitochondria revealed that both CUR-Mag-NLCs and curcumin have no specific mitochondrial toxicity.

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