Computational Modeling Analysis of Kinetics of Fumarate Reductase Activity and ROS Production during Reverse Electron Transfer in Mitochondrial Respiratory Complex II.

Reverse electron transfer in mitochondrial complex II (CII) plays an important role in hypoxia/anoxia, in particular, in ischemia, when the blood supply to an organ is disrupted and oxygen is not available. A computational model of CII was developed in this work to facilitate the quantitative analysis of the kinetics of quinol-fumarate reduction as well as ROS production during reverse electron transfer in CII. The model consists of 20 ordinary differential equations and 7 moiety conservation equations.

Mathematical Modeling of ROS Production and Diode-like Behavior in the SDHA/SDHB Subcomplex of Succinate Dehydrogenases in Reverse Quinol-Fumarate Reductase Direction.

Succinate dehydrogenase (SDH) plays an important role in reverse electron transfer during hypoxia/anoxia, in particular, in ischemia, when blood supply to an organ is disrupted, and oxygen is not available. It was detected in the voltammetry studies about three decades ago that the SDHA/SDHB subcomplex of SDH can have such a strong nonlinear property as a "tunnel-diode" behavior in reverse quinol-fumarate reductase direction. The molecular and kinetic mechanisms of this phenomenon, that is, a strong drop in the rate of fumarate reduction as the driving force is increased, are still unclear.

Computational Modeling Analysis of Generation of Reactive Oxygen Species by Mitochondrial Assembled and Disintegrated Complex II.

Reactive oxygen species (ROS) function as critical mediators in a broad range of cellular signaling processes. The mitochondrial electron transport chain is one of the major contributors to ROS formation in most cells. Increasing evidence indicates that the respiratory Complex II (CII) can be the predominant ROS generator under certain conditions.

Hysteresis and bistability in the succinate-CoQ reductase activity and reactive oxygen species production in the mitochondrial respiratory complex II.

The mitochondrial respiratory Complex II (CII) is one of key enzymes of cell energy metabolism, linking the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC). CII reversibly oxidizes succinate to fumarate in the TCA cycle and transfers the electrons, produced by this reaction to the membrane quinone pool, providing ubiquinol QH to ETC. CII is also known as a generator of reactive oxygen species (ROS).

Fatty acids and cholesterol in the liver cell nuclei of hibernating Yakutian ground squirrels.

The content of neutral lipids in tissue homogenates and liver cell nuclei of hibernating Yakutian ground squirrels was studied. In homogenates, hibernation increases the content of fatty acids and reduces the content of glycerides and cholesterol. When studying the liver cell nuclei of torpid winter ground squirrels, we detected a twofold increase in the content of fatty acids, cholesterol, and monoglycerides as compared to the "summer" ground squirrels.

Phospholipids of liver cell nuclei during hibernation of Yakutian ground squirrel.

In hibernating Yakutian ground squirrels S. undulatus, the content of total phospholipids in the nuclei of liver increased by 40% compared to that in animals in summer. In torpid state, the amount of sphingomyelin increased almost 8 times; phosphatidylserine, 7 times; and cardiolipin, 4 times.

[THE PHARMACOTHERAPEUTIC EFFICIENCY OF CYTOFLAVIN IN PATIENTS WITH DIABETIC FOOT SYNDROME: IMMEDIATE AND LONG-TERM RESULTS].

Immediate and long-term results of parenteral and oral administration of cytoflavin to patients with diabetic foot complicated by grade I and II trophic ulcers (Wagner classification) are considered with special reference to the assessment of reparative processes, normalization of the serum pro oxidant-antioxidant system, and improvement of clinical and instrumental bloodflow characteristics.

[Lipids in nuclei of neocortex neurons and glia under CNS-syndrome in rats].

The effect of a local exposure of rat heads to X-ray radiation at a dose of 200 Gy on the number of phospho- lipids and neutral lipids in the nuclear fraction ofneocortex neurons and glia has been investigated A decrease in the amount ofphosphatidylinositol and an increase in sphingomyelin in neuronal nuclei occurred 2 h after irradiation at the time of repair of locomotive disorders. The amount of phosphatidylcholine and phosphati- dylinositol dropped, and the amount of sphingomyelin and cholesterol increased in the nuclei ofglial cells of the neocortex. Sphingomyelin, phosphatidylinositol, phosphatidylcholine and cholesterol of neuronal nuclei are involved in the dynamics of the CNS syndrome in mammals.

[Lipids of neocortex after X-ray irradiation of the rat head at a dose of 200 Gy].

X-ray irradiation at a dose of 200 Gy with local exposure of the rat head induced the change of the lipid content in the neocortex tissue. The amount of phosphatidylinositol was decreased, the amount of free fatty acids, diglycerols, sphingomyelin was increased, and the amount of cholesterol had a growth trend in 2 h after X-ray exposition. The results testify in favor of participation of phosphatidylinositol- and sphingomyelin-relating signal systems and cholesterol in early stages of the cerebral radiation syndrome.

Lipids of nuclear fractions from neurons and glia of rat neocortex under conditions of artificial hypobiosis.

Lipid contents were studied in tissue and nuclei isolated from neurons and glia of neocortex of rats under conditions of normothermia and in the state of artificial hypobiosis caused by hypothermia-hypoxia-hypercapnia. Compared to the neocortex tissue, both nuclear fractions were fivefold impoverished in phospholipids and cholesterol and strongly enriched with mono- and diglycerides and fatty acids. The nuclear fractions from neurons and glia contained similar amounts of phospholipids, and only the cardiolipin content in the neuronal nuclei was lower than in the glial nuclei.

[The effect of X-rays and artificial hypotermia on lipids in rat neocortex].

Lipid content of tissue and of fraction of microsomes in neocortex of Wistar rats was studies under artificial hypothermia, after X-ray irradiation in dose 8 Gy under conditions of normothermia and artificial hypothermia in 48 h. The condition of artificial hypothermia get by cooling of rats to 15-18 degrees C. It was shown, that in fraction of microsomes of hypothermia rats the content of phosphatidylinositol was decreased, and in 48 h after cooling of rats the amount of protein, total and individual phospholipids was increased.

[The effect of hypothermia on the rat radioresistance].

The cooling of Wistar rats up to 15-19 degrees C under a condition hypoxia-hypercapnia increased the radioresistance with a dose reduction factor (DRF) of 1.4. To elucidate the mechanisms of hypothermia radioprotective effect was evaluated the functional state of rat neocortex using a electroencephalogram (EEG) as well as was studied the lipid composition of neocortex under the conditions of both normothermia and hypothermia.

Stiff-person syndrome following West Nile fever.

Background: Stiff-person syndrome is a rare autoimmune disorder associated with antibodies against glutamic acid decarboxylase (GAD), the key enzyme in gamma-aminobutyric acid synthesis. In most cases, a trigger cannot be identified.

Objective: To describe a 41-year-old man who developed stiff-person syndrome and antibodies to GAD following acute West Nile virus infection.

Synthesis of lipids in isolated nuclei from rat thymus and liver cells.

Synthesis of lipids was studied in isolated nuclei from rat thymus and liver cells. On incubation of the isolated nuclei with [2-14C]acetate and [1-14C]glycerol, the label was intensively incorporated into phospholipids and with a significantly lower intensity into fatty acids and cholesterol. Only trace amounts of radioactivity were detected in the lipids of chromatin prepared from isolated thymus nuclei after their incubation, and this suggested that lipids were mainly synthesized on the nuclear membrane.

[Nonmonotonous metabolic response of mammalian cells and tissues to ionizing radiation].

Changes in the activity of ornithindecarboxylase in various tissues and in the amount of catecholamine in rat hypothalamus by the action of acute and chronic ionizing radiation were studied. A nonmonotonous relationship between the metabolic parameters of animal tissues and cells and the radiation dose was revealed. It was assumed that the nonmonotonous character of the dose-response dependence results from the nonmonotonous time course of the metabolic response to irradiation.

Nuclear and chromatin lipids: metabolism in normal and gamma-irradiated rats.

The data on nuclear and chromatin lipid metabolism are reviewed. The amount of neutral lipids and phospholipids in nuclei of rat thymus, liver and neocortex neuron as well as the amount of lipids in rat thymus and liver chromatin are described. The metabolic responses of nuclear and chromatin lipids from thymus to different doses and dose rates of gamma-irradiation of rats are discussed.

Nonmonotonous Changes in Metabolic Parameters of Tissues and Cells under Action of Ionizing Radiation on Animal.

A nonmonotonous relationship between changes of metabolic parameters of tissues and cells of animal and radiation dose were discussed. Under acute irradiation of animals the nonmonotonous dose-response curve for metabolic parameters of tissues and cells were found. The nonmonotonous dose-response curves of metabolic and functional tissues and cells parameters were also revealed upon chronic irradiation of animals at a low dose-rate.

[Fatty acids metabolism of rat liver after extra-lethal gamma-irradiation].

The effect of acute gamma-irradiation of rats at super lethal doses from 25 to 270 Gy on the synthesis and amount of fatty acids, neutral lipids and phospholipids of liver was studied 48 h after gamma-irradiation. It was shown, that the synthesis of fatty acids, cholesterol, cholesterol ethers and phospholipids was activated 48 h after irradiation at 25-100 Gy, but the irradiation in the doses above 100 Gy inhibited the activation of lipid synthesis. The amount of fatty acids and neutral lipids of the rat liver decreased at 15-100 Gy.

[The amount of lipids in the rat liver in the late period after fractionated exposure to gamma radiation].

Remote effects of fractionated irradiation (6 Gy) on the amount of lipids in the rat liver were observed during a period of six months following irradiation. It was shown, that amount of cholesterol in rat liver decreased during the first months following irradiation, and after 6 months was normal. The content of phospholipids is not changed throughout the entire period of observation.

[Lipids from liver microsomes and mitochondria upon acute and chronic gamma-irradiation of rats].

It has been shown that acute gamma-irradiation of rats with 100 Gy and 270 Gy doses when the lipid synthesis in the liver is activated, produces changes in the lipid content in liver cell organelles. The amount of cholesterol and its esters in the microsomal fraction increases after 100 Gy but decreases after 270 Gy irradiation, the phospholipid content being unchanged. In the mitochondrial fraction the lipid content decreases 1 hour after 270 Gy irradiation but is expressed in a lower degree after 48 hours.

[Radiation changes in the lipid levels in liver and thymus chromatin of gamma-irradiated rats].

A study was made of the lipid content of liver and thymus chromatin of intact and gamma-irradiated (10 Gy) rats 10 and 40 min after irradiation. The composition of the chromatin-bound phospholipids was shown to differ from that of phospholipids of intact nuclei and a nuclear membrane by a much larger content of cardiolipin and sphingomyelin. A decrease in the lipid phosphorus level, increase in the amount of total cholesterol, and a 1.

[Turnover of chromatin-bound and membrane lipids in the liver and thymus of gamma-irradiated rats].

The turnover of nuclear and chromatin lipids from the liver and thymus of control and irradiated rats was studied by the incorporation of [14C]acetate. The chromatin-bound lipids were shown to possess a high metabolic activity which was especially well-pronounced in thymus cells. The higher specific radioactivity of the chromatin-bound lipids in comparison with that of intact nuclear lipids points to the structural uncoupling of chromatin lipids from other nuclear lipids.

[Metabolism of chromatin lipids in rat liver and thymus].

The amount and the ratio of individual chromatin-bound phospholipids and cholesterol from rat thymus and liver, tissues that are essentially different in the rate of proliferation, have been estimated. In liver chromatin the amount of phospholipids is two times and cholesterol three times higher than in thymus chromatin (per mg of chromatin DNA). As indicated by 2-14C-acetate incorporation the intensity of chromatin lipid metabolism is substantially higher than that of lipids of the intact nuclei (particularly in thymus).