Interactions of cardiolipin and lyso-cardiolipins with cytochrome c and tBid: conflict or assistance in apoptosis.
Explore the source record for details and available documents.
Apoptosis↗
Biomedical subjects
A A Kapralov
Publications and source records attributed to A A Kapralov.
The "pro-apoptotic genies" get out of mitochondria: oxidative lipidomics and redox activity of cytochrome c/cardiolipin complexes.
One of the prominent consequences of the symbiogenic origin of eukaryotic cells is the unique presence of one particular class of phospholipids, cardiolipin (CL), in mitochondria. As the product originated from the evolution of symbiotic bacteria, CL is predominantly confined to the inner mitochondrial membrane in normally functioning cells. Recent findings identified CL and its oxidation products as important participants and signaling molecules in the apoptotic cell death program. Early in apoptosis, massive membrane translocations of CL take place resulting in its appearance in the outer mitochondrial membrane. Consequently, significant amounts of CL become available for the interactions with cyt c, one of the major proteins of the intermembrane space. Binding of CL with cytochrome c (cyt c) yields the cyt c/CL complex that acts as a potent CL-specific peroxidase and generates CL hydroperoxides. In this review, we discuss the catalytic mechanisms of CL oxidation by the peroxidase activity of cyt c as well as the role of oxidized CL (CLox) in the release of pro-apoptotic factors from mitochondria into the cytosol. Potential implications of cyt c/CL peroxidase intracellular complexes in disease conditions (cancer, neurodegeneration) are also considered. The discovery of the new role of cyt c/CL complexes in early mitochondrial apoptosis offers interesting opportunities for new targets in drug discovery programs. Finally, exit of cyt c from damaged and/or dying (apoptotic) cells into extracellular compartments and its accumulation in biofluids is discussed in lieu of the formation of its peroxidase complexes with negatively charged lipids and their significance in the development of systemic oxidative stress in circulation.
Animals↗
Tocopherol modulates the effects of A23187, verapamil, and phorbol myristate acetate on RNA-polymerase activity of isolated rat liver nuclei.
Preincubation of rat liver nuclei with tocopherol decreased inhibition of RNA-polymerase activity of isolated rat liver nuclei by A23187, verapamil, and phorbol myristate acetate (PMA). In nuclei of vitamin E-deficient rats, A23187, verapamil, and PMA did not inhibit label incorporation into RNA with and without tocopherol. A23187, verapamil, and PMA did not inhibit the activity of nuclei treated with 1% Triton X-100; tocopherol activated RNA synthesis but co-administration of A23187 or verapamil and tocopherol had no effect and the combination of tocopherol and PMA inhibited RNA-polymerase activity by 25%. The effect of the combination of verapamil and PMA in the presence of free tocopherol was different from the effect of these compounds assayed in the presence of the complex of tocopherol with tocopherol-binding protein.
Animals↗
[Effect of alpha-tocopherol and ubiquinone on mitochondrial RNA polymerase activity. The role of tocopherol-binding proteins].
It has been shown that alpha-tocopherol within the complex with tocopherol-binding proteins, in contrast with free tocopherol, decreases the RNA-polymerase activity in isolated rat liver mitochondria. Both free and complexed to proteins alpha-tocopherol increases the RNA-polymerase activity in isolated nuclei. The effect of alpha-tocopherol is conditioned mostly by the nature of the tocopherol-binding proteins. It has been established that ubiquinone complexed to tocopherol-binding proteins from mitochondria can also change the level of RNA synthesis. The effect of alpha-tocopherol and ubiquinone are not additive.
Animals↗
[Effect of vitamin E on transcription in isolated nuclei and rat liver chromatin in normal status and in E-hypovitaminosis].
The effect of alpha-tocopherol on the RNA-polymerase activity in isolated rat nuclei and chromatin from normal and E-deficient rats and the possible role of tocopherol-binding proteins in this process were studied. Some differences in the RNA-polymerase activities of the nuclei were found; however, in vitro added alpha-tocopherol had no effect on the level of the label incorporation into RNA. No effect of alpha-tocopherol on this process was observed after addition of cytosol either. Analysis of chromatins from normal and E-deficient rats revealed no differences in their RNA-polymerase activities. In vitro added alpha-tocopherol increased the RNA-polymerase activity of normal (but not of vitamin E-deficient) rats. Some differences in the RNA-polymerase activities were noted after addition to the incubation medium of the Triton X-100-solubilized nuclear fraction specifically binding alpha-tocopherol. This effect was enhanced in the presence of exogenous alpha-tocopherol. The susceptibility of chromatin from normal and E-deficient rats to DNAse I hydrolysis was also found to be different. It was concluded that vitamin E can influence the RNA-polymerase activity of the nuclei and chromatin as well as the chromatin structure and that alpha-tocopherol-binding proteins are necessary for the vitamin E effect on the RNA-polymerase activity to be manifested.
Animals↗
[Role of the cytosolic factor in the interaction of [3H] alpha-tocopherol with rat liver nuclei].
A protein fraction (Mr = 30-70 kD) specifically binding [3H]alpha-tocopherol was isolated from rat liver cytosol. Using high performance ion exchange chromatography, this fraction was separated into acid and alkaline protein subfractions. Acid proteins make up to 41% of the total protein pool and they bind the label 8 times more intensively than the alkaline ones. Cytosol and its protein fraction with an average molecular mass increase 2.2-2.5-fold the binding of labeled vitamin E to isolated liver nuclei. It is concluded that the cytosolic proteins having a medium molecular mass are involved in tocopherol interaction with the nuclei.
Animals↗
[Effect of neuromediating and neuroblockading hormones on the RNA synthesis in the rat liver nucleus].
It was shown that rRNA and HnRNA synthesis in rat liver nuclei does not change-within 30 min after intraperitoneal injection of acetylcholine (0.005 mg per 100 g of body weight) but decreases after injection of norepinephrine and epinephrine (0.05 mg per 100 g of body weight). The synthesis of rRNA (but not of HnRNA) increases after injection of hydrocortisone (2,5 mg per 100 g of body weight). The synthesis of HnRNA (but not of rRNA) increases after injection of ACTH1-24 (3 ME per 100 g of body weight) and oxytocin (1 ME per 100 g of body weight). The synthesis of rRNA decreases after injection of propranolol and atropine (0.5 mg per 100 g of body weight). At the same time, the synthesis of HnRNA does not change thereby. The inhibitory effect of propranolol and atropine was corrected by electrostimulation of hypothalamus. The content of cAMP and Ca2+ and the phosphorylation degree of nuclear proteins are increased after stimulation of hypothalamus. The phosphorylation of nuclear proteins is increased by 10(-8)-10(-6) M cAMP. The synthesis of RNA in liver nuclei is increased by 10(-6) M cAMP only after addition of cytosol. In this case the activity of RNA-polymerase II increases in a greater degree than that of RNA-polymerase I + III. It is assumed that the regulatory mechanisms of rRNA and HnRNA synthesis are different. The role of hypothalamus electrostimulation, neurotransmitters, hormones, and cAMP in the mechanisms of RNA synthesis in rat liver nuclei is discussed.
Acetylcholine↗
[Effect of protein S-100 on phosphorylation of nuclear proteins of cells of rat brain and liver].
The effect of acidic neurospecific protein S-100 on the phosphorylation of brain and liver nuclear proteins with 1 and 10 microM ATP was investigated. It was shown that protein S-100 increases the phosphorylation of brain nuclear proteins, while antigen D, another acidic neurospecific protein half-identical to 14-3-2 protein, inhibits this process. Ca2+ and cAMP at concentration of 10(-6) M do not affect the phosphorylation of brain nuclear proteins. In control assays the tracer 32P is presumably incorporated into high molecular weight nuclear protein fractions (Mr greater than 40000). After addition of protein S-100 the tracer is mainly incorporated into these proteins as well independently of ATP concentration (1 or 10 microM). The phosphorylation of nuclear proteins with molecular weights above 100000 is mostly increased in this case. At ATP concentration of 1 microM protein S-100 decreases histone phosphorylation 2.3 times but does not affect that of non-histone proteins. However, at 10 microM ATP the inhibitory action of this protein on histone phosphorylation is absent. The possible mechanisms of protein S-100 action on nuclear proteins phosphorylation are discussed.
Animals↗
[Turnover of chromatin proteins in rat liver during induction of RNA synthesis by electrostimulation of the hypothalamus].
It has been shown that the induction of D-RNA synthesis in rat liver nuclei by electrostimulation of hypothalamus is accompanied by a decrease in chromatin protein synthesis and an increase in phosphorylation and acetylation of chromatin proteins. The decrease of the histone synthesis is mainly due to the decrease of [14C]lysine and [14C]alanine incorporation into histones H1 and H4. The relationship between H1, H2b-H3, H2a and H4 histone fractions remains unchanged. Electrostimulation of hypothalamus increases acetylation of H2a and H4 histone fractions and phosphorylation of all histones with the exception of histone H1.
Acetylation↗
[Role of Ca ions and protein kinase C in the action of vitamin E on respiratory burst of neutrophils and blast transformation of lymphocytes].
It was shown that vitamin E decreased the stimulating role of oxidative burst activators which influenced on Ca(2+)-dependent mechanisms (A23187, verapamil, FMLP). Jointly addition of this vitamin and blood plasma contained tocopherol-binding proteins influenced on mechanisms associated with protein kinase C. It was shown that Ca ions can also take part in tocopherol's action on blast transformation of lymphocytes.
Calcimycin↗
[Incorporation of [3H]alpha-tocopherol into isolated nuclei and its binding by rat liver chromatin].
The investigation of inclusion of [3H]alpha-tocopherol to isolated rat liver nuclei has revealed its nonspecific character. The presence of cytosol is necessary for specific interaction of alpha-tocopherol with nuclei. After the centrifugation of preliminarily labeled chromatin the most quantity of tocopherol was bound with oligonucleosomes and pelleted chromatin. It is supposed, that the preservation of supernucleosomes level of chromatin folding was necessary for the interaction of alpha-tocopherol with chromatin.
Animals↗
[Comparative study of the effect of alpha-tocopherol, its synthetic metabolite and ionol on dexamethasone-induced apoptosis in rat thymocytes].
alpha-Tocopherol was found to decrease the level of rat thymocytes DNA fragmentation and to increase the viability of these cells under apoptosis induction by dexamethazone. So the antiapoptotic role of this vitamin is suggested. In contrast to alpha-tocopherol synthetic antioxidant ionol and alpha-tocopherylacetate, contained only 6 carbon atoms in its isoprenoid side chain caused the cell death from necrosis. This process preceded the apoptosis stimulated by dexamethazone.
Animals↗
[Effect of brain cytosol proteins of embryonal and adult animals on RNA-polymerase activity of isolated brain nuclei].
Cytosol and its fractions obtained by the precipitation with ammonium sulphate and ion-exchange chromatography have been studied for their effect on the RNA-polymerase activity of isolated nuclei. We observed the discrepancies in the action of total cytosol of embryonal, newborn or adult animals on the label's incorporation in RNA. It was found that some fractions increased DNA-polymerase activity of isolated nuclei in cattle embryonal cytosol. The same fractions obtained from adult cytosol did not act in such a way. It was found that most fractions obtained from cytosol of adult brain inhibited the RNA-polymerase activity of brain nuclei.
Aging↗
[Vitamin E and apoptosis].
The literature data concerning the participation of tocopherol in apoptosis are discussed. Acting as antioxidant this vitamin exerts a complex effect on apoptosis mechanisms. Its action on this process is caused by involvement of some different mechanisms transducing the apoptotic signal. Among them are caspase and Fas-receptor activation, sphingosine metabolism, processes carried out in nuclei and mitochondria and signal transduction pathways. The specific mechanisms connected with interaction of this vitamin with tocopherol-binding proteins may be also involved in this vitamin action.
Animals↗
[Changes in protein, lipid composition, DNA- and RNA- polymerase activity of the chromatin fraction and the nuclear matrix of the rat liver in hypovitaminosis E].
E-hypovitaminosis-induced antioxidant deficiency in rats causes changes in some properties of nuclear structures of the liver cells, i.e. fractions of transcriptionally active and repressed chromatin and nuclear matrix. Changes are found in the protein spectrum of the fraction of transcriptionally active chromatin and nuclear matrix. Lipids of transcriptionally active and repressed chromatin fractions may be peroxidated when this process is stimulated in the NADPH- and ascorbate-dependent systems. In antioxidant deficiency these processes are intensified in the fractions of repressed chromatin. E-hypovitaminosis leads to changes in the fatty acid spectrum of chromatin fractions which correlated with the shifts in the process of lipid peroxidation. Antioxidant deficiency produces changes in the activities of endogenous DNA- and RNA-polymerases in chromatin fractions and in the nuclear matrix. In the fraction of the transcriptionally active liver chromatin of E-deficient animals the endogenous total DNA-polymerase activity and the activity of DNA-polymerases alpha and beta decrease, while in the fractions of repressed chromatin the total RNA-polymerase activity increases. In E-hypovitaminosis the endogenous DNA- and RNA-polymerase activities in the nuclear matrix decrease. Addition of alpha-tocopherol to the preparations of the isolated nuclear matrix results in an increase of the DNA- and RNA-polymerase activities which is more vivid in preparations made of the E-hypovitaminous animal liver.
Animals↗
[Tocopherol-binding proteins in membranes of rat liver mitochondria].
The use of the adsorption chromatography on the hydroxyl apatite makes it possible to yield and partly purify the triton X-100-solubilized mitochondrial protein fraction of the rat liver able to bind specifically [3H]-alpha-tocopherol. The method permits removing simultaneously both free detergent and [3H]-alpha-tocopherol from the protein mixture without disturbance of the established equilibrium. When compared with methods used for the removal of free hydrophobic ligands in the in vitro binding experiments, the applied method is the most effective.
Animals↗
[Chromatin proteins binding vitamin E].
It was discovered that alpha-tocopherol binding with isolated chromatin is specific only when fraction of tocopherol-binding proteins from a nuclear extract with 1% triton X-100 is present. During the chromatography of chromatin incubated with [H] alpha-tocopherol on hydroxyapatite a specific binding activity was present only in fraction eluted with 2M NaCl + 5M urea. Quantitative changes in the protein content of this fraction during a hypovitaminosis are found. It is shown that vitamin E can effect the RNA polymerase activity of a nuclear matrix in the in vitro assays. It is suggested that the presence of tocopherol-binding proteins of chromatin in necessary for such an action of alpha-tocopherol.
Chromatin↗
[Role of S-100 protein in the function of brain cell nuclei].
Data on physico-chemical properties and functional role of protein S-100 have been generalized. An analysis of literary data permits making a conclusion that the protein interaction with Ca2+ ions plays great part in its action mechanisms. Data are presented on the properties of the family of Ca-binding proteins similar to protein S-100 as to their structure. Peculiar attention is paid to the analysis of this protein function in the cellular nucleus, changing the degree of proteins phosphorylation and RNA synthesis.
Animals↗