N V Khunderyakova

Institute of Theoretical and Experimental Biophysics, Pushchino-na-Oke, MO, Russia

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Publications (11)19.4 Total impact

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    ABSTRACT: Lymphocytes in blood smears of children diagnosed with cancer have been investigated and compared to those of healthy children (matching controls). The conventional hematological procedure for smear staining was used to assess the blood formula and lymphocyte indices, and a new staining method involving incubation of cells in a biochemical medium for 1 h was used to assess the activity of succinate dehydrogenase, lactate dehydrogenase, and the ratio of the activities of these enzymes characterizing the interaction of respiration and glycolysis. A dramatic increase of the size of lymphocytes obtained from cancer patients was detected when lactic acid was added to the incubation medium for the biochemical reaction. This effect was neither observed when succinic acid was added nor when blood smears from healthy children of the control group were tested. Structural changes in the patients’ cells were associated with changes in the activity of the enzymes under investigation. The cytobiochemical test that was developed allows increasing diagnostic sensitivity upon assessment of the patients’ state and can contribute to more efficient treatment of malignant tumors.
    No preview · Article · Nov 2015 · Biophysics
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    ABSTRACT: Using an original cytobiochemical method to study oxidation in mitochondria, preserving their native network organization within cells in a blood smear, we have revealed a hyperactive state of succinate dehydrogenase that arises in the organism under physiological stress. This is generally consistent with the notion of non-equilibrium state of enzymes during their activity. The mechanism moderating the succinate dehydrogenase hyperactivity is based on full-fledged functioning of α-ketoglutarate dehydrogenase, sup-ported by oxidation of isocitrate.
    No preview · Article · Jan 2013 · Biophysics
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    ABSTRACT: Conditions for the realization in rats of moderate physiological stress (PHS) (30-120min) were selected, which preferentially increase adaptive restorative processes without adverse responses typical of harmful stress (HST). The succinate dehydrogenase (SDH) and α-ketoglutarate dehydrogenase (KDH) activity and the formation of reactive oxygen species (ROS) in mitochondria were measured in lymphocytes by the cytobiochemical method, which detects the regulation of mitochondria in the organism with high sensitivity. These mitochondrial markers undergo an initial 10-20-fold burst of activity followed by a decrease to a level exceeding the quiescent state 2-3-fold by 120min of PHS. By 30-60min, the rise in SDH activity was greater than in KDH activity, while the activity of KDH prevailed over that of SDH by 120min. The attenuation of SDH hyperactivity during PHS occurs by a mechanism other than oxaloacetate inhibition developed under HST. The dynamics of SDH and KDH activity corresponds to the known physiological replacement of adrenergic regulation by cholinergic during PHS, which is confirmed here by mitochondrial markers because their activity reflects these two types of nerve regulation, respectively. The domination of cholinergic regulation provides the overrestoration of expenditures for activity. In essence, this phenomenon corresponds to the training of the organism. It was first revealed in mitochondria after a single short-time stress episode. The burst of ROS formation was congruous with changes in SDH and KDH activity, as well as in ucp2 and cox3 expression, while the activity of SDH was inversely dependent on the expression of the gene of its catalytic subunit in the spleen. As the SDH activity enhanced, the expression of the succinate receptor decreased with subsequent dramatic rise when the activity was becoming lower. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaption and therapy.
    Full-text · Article · Jul 2012 · The international journal of biochemistry & cell biology
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    ABSTRACT: The comparison of succinate dehydrogenase activity(SDH) was carried out in the presence of succinate(SUC) in commonly used millimolar("substrate" ) concentrations that significantly exceeds the SUC content in tissues,and in micromolar concentrations really present in the organism,currently called "signaling" concentrations. This name reflects the function of SUC,a substrate of oxidation,as a signaling molecule regulating physiological processes. Regulatory signaling action of SUC occurs in significantly lower concentrations,at least 1000 times lower than "substrate" concentration. Signaling action is related to adrenergic regulation including SDH as its target. It is realized via specific SUC receptor,GPR91. Here the SDH activity was studied under different physiological conditions in rat and human using new cytobiochemical(CBCH) method,which sensitively reveals changes in the organism due to the preservation of the native state of mitochondrial network. SDH activity was measured in lymphocytes in blood smear by nitro blue tetrazolium(NBT) reduction due to oxidation of added and endogenous substrates. The high statistical validity is an additional advantage of the CBCH method,because every separate value is measured by videomicroscopic scanning of multitude of stained objects(mitochondria),200-700 in one sample containing images of 30 lymphocytes of an individual. High sensitivity of CBCH method allowed detection of the SDH activity with SUC being in both millimolar and micromolar concentrations. Activation of SDH was revealed upon increase in adrenergic regulation in the norm(by adrenaline administration) and in acute phase of hypertension,followed by inhibition under arterial pressure stabilization by hypotensive preparations,which are adrenaline receptor blockers and internal regulators at chronic stages. The use of micromolar SUC concentrations reveals changes in SDH activity in the organism related to the differences in the physiological states more efficiently than the use of millimolar concentrations,which activate SDH and smooth over the development of inhibition under pathology progressing. While SDH activity measured at millimolar SUC concentrations was depressed,a significant rise in NBT reduction was observed in the presence of micromolar concentrations. This suggests that the effect of signal(but not substrate) concentrations can be realized through generation of superoxide and hydrogen peroxide,which possess vitally beneficial regulatory effects in micromolar concentrations in mitochondria.
    No preview · Article · Jan 2012 · Biologicheskie membrany
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    Full-text · Article · Jul 2010 · Biochimica et Biophysica Acta (BBA) - Bioenergetics
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    Full-text · Article · Jul 2010 · Biochimica et Biophysica Acta (BBA) - Bioenergetics
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    ABSTRACT: We measured the activity of mitochondrial succinate dehydrogenase (SDH) within cells, in media with near-physiological composition, in lymphocytes immobilized in a blood smear on glass. SDH activity was studied in newborn rats characterized by natural hyperadrenergic status and also in adult animals injected with epinephrine. In most newborns very high activities were recorded, which exceeded the activities in adults at rest 7-8-fold or 3-fold according to the conventional calculation, or more than 30- and 6-fold according to our more precise calculation. The findings support our concept about a selective interaction between adrenergic stimulation and oxidation of succinic acid. According to this concept, epinephrine and norepinephrine specifically activate oxidation of succinic acid, whereas blood micromolar concentrations of the latter stimulate the release of catecholamines (the receptor-mediated signaling effect). This interaction is half of a substrate-hormonal regulatory system responsible for connection of vegetative nervous system with oxidation in mitochondria of the innervated organs. The increase in succinate oxidation by catecholamines includes activation of the faster pathways of succinate generation than the complete Krebs cycle, in particular, the glyoxylate cycle that is shown in the newborn rats in the present study.
    No preview · Article · Apr 2008 · Biochemistry (Moscow)
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    T. V. Sirota · O. P. Yelisyeyeva · N. V. Khunderyakova · O. A. Makhotina
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    ABSTRACT: Respiration parameters of liver mitochondria (MCh) in rats fed with amaranth seed oil for 3 weeks have been evaluated. Thirty minutes before decapitation, adrenaline was injected intraperitoneally at a low dose (350 μg/kg body weight) to both control and experimental animals. It was shown that in animals that were injected with adrenaline and did not receive oil, the rate of phosphorylating respiration increased by 32% and phosphorylation time decreased by 22% upon oxidation of succinate; upon oxidation of α-ketoglutarate in the presence of the succinate dehydrogenase inhibitor malonate, phosphorylating respiration was activated by 23%. The respiration of MCh upon oxidation of succinate + glutamate and α-ketoglutarate in the absence of malonate was not affected by adrenaline. The intake of oil markedly activated almost all parameters of mitochondrial respiration in experimental rats upon oxidation of all above-listed substrates in both coupled and uncoupled MCh. However, phosphorylation time was close to the control value (upon oxidation of succinate) or increased (upon oxidation of α-ketoglutarate in the presence and absence of malonate). The injection of adrenaline to animals receiving oil did not affect the oil-activated respiration of MCh oxidizing the substrates used; however, phosphorylation time in all groups of animals decreased. Ca2+ capacity of MCh in rats receiving amaranth oil did not change. Thus, our data show that feeding of rats with amaranth oil activates mitochondrial respiration and prevents MCh hyperactivation induced by adrenaline.
    Full-text · Article · Feb 2008 · Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology
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    ABSTRACT: It has been shown that a three-week feeding of rats with oil derived from seeds of amaranth (Amaranthus cruentus L.) leads to a moderate activation of respiration of coupled and uncoupled rat liver mitochondria (MCh) that oxidize succinate and succinate + glutamate, as well as α-ketoglutarate and α-ketoglutarate + malonate. In animals receiving the amaranth oil, the injection of adrenaline did not affect the oil-activated respiration of MCh during succinate oxidation; i. e., animals prepared by an oil-enriched diet were resistant to the action of adrenaline, which prevented from possible hyperactivation of mitochondrial functions. In the group of control animals, which received no oil, the injection of adrenaline activated the rate of phosphorylating respiration of MCh during oxidation of succinate or succinate + glutamate: the rate of oxygen uptake in state 3 respiration (by Chance) increased, and the phosphorylation time decreased. The injection of adrenaline did not affect the parameters of respiration of MCh that oxidize α-ketoglutarate; however, in the presence of malonate, the oxidation of α-ketoglutarate in state 3 and uncoupled respiration have shown mild but significant increase in response to adrenaline. In animals receiving the amaranth oil, the oil-induced activation of respiration of MCh in response to adrenaline retained but did not increase; however, the phosphorylation time significantly decreased. Thus, concentrated oil of seeds activates the respiration of MCh. In addition, it enhances an energetic function of MCh, which prevents from the hyper-activation of mitochondrial respiration by adrenaline. Therefore an activation of energetic function of MCh by amaranth oil could explain its adaptogenic effect on rats.
    Full-text · Article · Jan 2007
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    ABSTRACT: The role of impairment of general oxidative and energy metabolism in pathogenesis of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) and their correction by (1-adrenoblocker alfuzosin was studied. One group of patients (N = 126) was examined by standard methods for determination of the severity of LUTS by IPSS and mean effective volume of urinary bladder (MEVUB). In the second group (N = 29) in addition to functional examinations, metabolic indicators in blood were measured: antioxidant activity (AOA) and succinate dehydrogenase activity (SDA). Severity of LUTS depends greatly on the MEVUB. It was the first to show a practically complete correlation between LUTS, AOA and SDA. Severity of LUTS exactly correlates with indicators of oxidative and energy metabolism. In patients with more heavy LUTS, lowest AOA and SDA values were found. In the course of effective treatment, both phenomena developed an improvement of clinical symptoms and a rise of biochemical parameters. Close correlation between functional and metabolic phenomena is evidence of an essential role of metabolic mechanisms in the pathogenesis of LUTS with BPH. This opens perspectives to use antioxidants and energy metabolism activators for correction of UB dysfunction in patients with BPH.
    No preview · Article · Nov 2003 · Mitochondrion
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    ABSTRACT: Assay Assay & & Drug Drug Amberen contains 50% ammonium succinate (the most powerful energy source in mitochondria) with minor additions of other metabolites. Amberen alleviates most pathological symptoms of the menopausal syndrome. At the level of the whole organism Amberen promotes correction of energetic processes that are highly unstable during menopause. A key part of Amberen action is the increase in sensitivity of the hypothalamus and peripheral endocrine glands to regulatory signals. It was previously shown that Amberen produces a significant influence on the endocrine system; in particular, it promotes restoration of the estrous cycle in old female rodents while increasing weight and calcium content of femur bones, thus producing a "rejuvenating" effect. Placebo-controlled clinical studies have shown that Amberen administration drastically reduces the severity of the majority of pathological symptoms of the menopausal syndrome and significantly increases blood estradiol level. Amberen was also shown to have beneficial effect on some of the neurovegetative and psycho-emotional symptoms, such as hot flushes, headache and a feeling of anxiety [10].
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