Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured the contribution of mitochondrial nitric oxide synthase (mtNOS) and respiratory chain enzymes to reactive nitrogen species (RNS) production. Diaminofluorescein (DAF) was applied for the assessment of RNS production in isolated mouse brain, heart and liver mitochondria and also in a cultured neuroblastoma cell line by confocal microscopy and flow cytometry. Mitochondria produced RNS, which was inhibited by catalysts of peroxynitrite decomposition but not by nitric oxide (NO) synthase inhibitors. Disrupting the organelles or withdrawing respiratory substrates markedly reduced RNS production. Inhibition of complex I abolished the DAF signal, which was restored by complex II substrates. Inhibition of the respiratory complexes downstream from the ubiquinone/ubiquinol cycle or dissipating the proton gradient had no effect on DAF fluorescence. We conclude that mitochondria from brain, heart and liver are capable of significant RNS production via the respiratory chain rather than through an arginine-dependent mtNOS.
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PMID:Mitochondria produce reactive nitrogen species via an arginine-independent pathway. 1651 1

In acute experiments performed on rats placed in heat-chamber (40 degrees C, 30- and 60-minutes-long exposure), an increase in NADPH-diaphorase (NADPH-d) and succinate dehydrogenase (SDH) activities were found in the neurons of intramural ganglia of the right atrium, while SDH and lactate dehydrogenase (LDH) activities were increased in cardiomyocytes. Hormone-producing cardiomyocytes, containing atrial natriuretic peptide, had numerous large secretory granules under the sarcolemma close to the microvessels. In contractile cardiomyocytes, the signs of early stage of apoptosis were observed including the subsarcolemmal accumulation of small mitochondria and cytoplasmic invaginations into the nucleus. Prolonged heating (37 degrees C, 4 h daily) led to an increased activities of NADPH-d and SDH in neurons of intramural ganglia of the right atrium and of NADPH-d and LDH in cardiomyocytes. Secretory granules in hormone-producing cardiomyocytes were small and reduced in number. Cardiomyocytes showing the signs of the late stage of apoptosis (with nuclear and cytoplasmic condensation) were demonstrated.
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PMID:[Structural and functional changes in the right atrium of the rats induced by short- and long-term heat stress]. 1666 45

Nitric oxide (NO) supposedly derived via L-arginine-NO synthase (NOS) pathway has been implicated in inhibiting steroidogenesis by binding the heme moiety of steroidogenic enzymes. Previously, nitrite, and to a lesser extent nitrate ions inhibited steroidogenesis via NO by hitherto unknown reduction mechanism. Recently, a putative mammalian nitrite reductase activity ascribed to complex III of mitochondrial respiratory chain complexes (MRCC) has been reported, where MRCC inhibitors reduced NO production from nitrite variably. We thus studied the effects of MRCC inhibitors on testosterone production in mouse Leydig tumor cells (MLTC-1) without (basal) or with human chorionic gonadotropin (hCG) stimulation. In stimulated MLTC-1, MRCC inhibitors decreased testosterone production, order being: complex III (antimycin A and myxothiazol) > complex I (rotenone) > complex II (thenoyltrifluoroacetone), while cAMP production increased inversely. In unstimulated MLTC-1, MRCC inhibitors in same order, increased basal testosterone production, which correlated inversely with the percentage inhibition of NO production, with one exception; while antimycin A did not inhibit NO production in the nitrite reductase study mentioned above, it increased basal testosterone production in the present study. While MLTC-1 expressed mRNA for endothelial and neuronal, but not inducible NOS, various stimulators and inhibitors of L-arginine-NOS pathway had no effect on basal testosterone production in MLTC-1 or fresh Balb/c Leydig cells. Moreover, hCG increased nitrate uptake into MLTC-1, which suggests the gonadotropin aids nitrite and nitrate ions in their steroidogenesis inhibitory activity. In conclusion, this study supports the existence of a surrogate mammalian nitrite reductase and the dormancy of L-arginine-NOS pathway in MLTC-1.
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PMID:Evidence for nitrite reductase activity in intact mouse Leydig tumor cells. 1695 82

The epidermis of vertebrates is the body's principal barrier against environment and its possible contaminants. The presence of keratins, as well as specific detoxifying molecules or enzyme activities, in the various epidermis layers is believed to be involved in providing protection from harmful environmental influences. Anuran integument is poorly hornified and thus permeable to some endogenous and exogenous compounds and thus serves as a good bioindicator of overall environmental conditions. In the present investigation, we studied the epidermis of Rana kl. esculenta adult specimens collected at two different rice fields, relatively unpolluted and heavily polluted, respectively. Environmental pollution was assayed by chemical analysis performed on both sediments and animals. We evaluated the structural aspects of the epidermis at both light and electron microscopy levels and the pattern of keratinization by immunohistochemistry. Furthermore, we studied the activities of some enzymes (acid and alkaline phosphatase, nitric oxide synthase-related nicotinamide adenine dinucleotide phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, catalase, nonspecific esterases, and succinic dehydrogenase) involved mainly in membrane transport, xenobiotics, and oxidative metabolism. Compared with controls, in polluted animals we found the following results: (1) an increase in pollutant levels (i.e., cadmium, mercury, and lead); (2) less keratinized superficial cells in the epidermis; and (3) changes in most enzyme activities in keratinocytes and mitochondria-rich cells (particularly glucose-6-phosphate dehydrogenase and esterases, both important to counteract oxidative and toxic stress). Taken as a whole, the present data indicate the morphofunctional plasticity of the frog epidermis in response to environmental contamination.
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PMID:Morphofunctional evidence of changes in principal and mitochondria-rich cells in the epidermis of the frog Rana kl. esculenta living in a polluted habitat. 1699 33

Many biological properties have been attributed to ruthenium complex I (trans-[RuCl(2)(nic)(4)]) and ruthenium complex II (trans-[RuCl(2 )(i-nic)( 4)]) including nitric oxide synthase inhibition. In this study, we evaluated pharmacological effects of these complexes on anxiety and memory formation. Memory was evaluated with inhibitory avoidance and habituation to an open-field and anxiety was tested with elevated plus-maze. Adult male Wistar rats (250 to 350 g) received intraperitoneal injections of vehicle, ruthenium complex I (45.2, 90.4, or 180.7 mumol/kg), or ruthenium complex II (0.08, 4.5, or 13.6 mumol/kg) 30 min prior open-field training or elevated plus-maze test and 30 min or 0 h after training. No effects were observed in the anxiety parameters and habituation to an open-field. The ruthenium complexes impaired memory retention compared with vehicle group in the inhibitory avoidance, as when administrated 30 min prior as immediately after training. The memory impairment induced by ruthenium complexes may be due to their nitric oxide synthase inhibition capacity.
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PMID:Pharmacological activity of ruthenium complexes trans-[RuCl(2)(L)4] (l = nicotinic or i-nicotinic acid) on anxiety and memory in rats. 1710 55

The mitochondrial toxin, 3-nitropropionic acid (3-NP), is a specific inhibitor of succinate dehydrogenase, complex II in the mitochondrial respiratory chain. The aim of our study was to determine the relationship between inhibition of mitochondrial complex II and dopamine (DA) metabolism and its transport into rat striatal synaptosomes after exposure to 3-NP. The study was carried out using spectrophotometric, radiochemical and HPLC methods. Our data showed that inhibition of succinate dehydrogenase by intraperitoneal (i.p.) injection of 3-NP (cumulated dose 100 mg/kg in 4 days) significantly affected DA metabolism, leading to the accumulation of its metabolites, 3,4-dihydroxylphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the rat striatum. These experimental conditions had no effect on free radical dependent lipid peroxidation in the brain. In vitro experiments revealed that DA and DOPAC significantly decrease lipid peroxidation in the brain homogenate. Moreover, 3-NP significantly inhibited [3H]DA uptake into striatal synaptosomes by specific dopamine transporter (DAT). The scavengers of superoxide radical (O2-) Tempol and Trolox had no effect on DAT function, but the nitric oxide synthase (NOS) inhibitor N w-nitro-L-arginine (100 microM) prevented 3-NP-evoked DAT down-regulation. In summary, our results indicate that inhibition of mitochondrial complex II by 3-NP enhances DA degradation and decreases its uptake into synaptosomes. It is suggested that NO and energy failure are responsible for alteration of the dopaminergic system in the striatum.
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PMID:Inhibition of mitochondrial complex II affects dopamine metabolism and decreases its uptake into striatal synaptosomes. 1718 49

In the present study we investigated the effect of intrastriatal administration of 150 nmol quinolinic acid to young rats on critical enzyme activities of energy production and transfer, as well as on 14CO2 production from [1-14C]acetate at distinct periods after quinolinic acid injection. We observed that quinolinic acid injection significantly inhibited complexes II (50%), III (46%) and II-III (35%), as well as creatine kinase (27%), but not the activities of complexes I and IV and citrate synthase in striatum prepared 12 h after treatment. In contrast, no alterations of these enzyme activities were observed 3 or 6 h after quinolinic acid administration. 14CO2 production from [1-14C]acetate was also significantly inhibited (27%) by quinolinic acid in rat striatum prepared 12 h after injection. However, no alterations of these activities were observed in striatum homogenates incubated in the presence of 100 microm quinolinic acid . Pretreatment with the NMDA receptor antagonist MK-801 and with creatine totally prevented all inhibitory effects elicited by quinolinic acid administration. In addition, alpha-tocopherol plus ascorbate and the nitric oxide synthase inhibitor l-NAME completely abolished the inhibitions provoked by quinolinic acid on creatine kinase and complex III. Furthermore, pyruvate pretreatment totally blocked the inhibitory effects of quinolinic acid injection on complex II activity and partially prevented quinolinic acid-induced creatine kinase inhibition. These observations strongly indicate that oxidative phosphorylation, the citric acid cycle and cellular energy transfer are compromised by high concentrations of quinolinic acid in the striatum of young rats and that these inhibitory effects were probably mediated by NMDA stimulation.
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PMID:Evidence that quinolinic acid severely impairs energy metabolism through activation of NMDA receptors in striatum from developing rats. 1723 Jun 42

We show here that the nitric oxide (NO)-detoxifying Hmp flavohemoprotein increases by 3-fold the transcription of the Salmonella pathogenicity island 2 (SPI2) in macrophages expressing a functional inducible NO synthase (iNOS). However, Hmp does not prevent NO-related repression of SPI2 transcription in IFNgamma-primed phagocytes, despite preserving intracellular transcription of sdhA sdhB subunits of Salmonella succinate dehydrogenase within both control and IFNgamma-primed phagocytes. To shed light into the seemingly paradoxical role that Hmp plays in protecting intracellular SPI2 expression in various populations of macrophages, N(2)O(3) was quantified as an indicator of the nitrosative potential of Salmonella-infected phagocytes in different states of activation. Hmp was found to prevent the formation of 300nM N(2)O(3)/h/bacteria in IFNgamma-primed macrophages, accounting for about a 60% reduction of the nitrosative power of activated phagocytes. Utilization of the vacuolar ATPase inhibitor bafilomycin indicates that a fourth of the approximately 200nM N(2)O(3)/h sustained by IFNgamma-primed macrophages is generated in endosomal compartments via condensation of HNO(2). In sharp contrast, control macrophages infected with wild-type Salmonella produce as little N(2)O(3) as iNOS-deficient controls. Collectively, these findings indicate that the NO-metabolizing activity of Salmonella Hmp is functional in both control and IFNgamma-primed macrophages. Nonetheless, a substantial amount of the NO generated by IFNgamma-primed macrophages gives rise to N(2)O(3), a species that not only enhances the nitrosative potential of activated phagocytes but also avoids detoxification by Salmonella Hmp.
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PMID:N(2)O(3) enhances the nitrosative potential of IFNgamma-primed macrophages in response to Salmonella. 1808 77

Widely used in the past against termites and soil insects, the chlorinated insecticide heptachlor (H) is a toxic contaminant which represents a risk for both terrestrial and aquatic organisms. Like many organochlorine pesticides, heptachlor and heptachlor epoxide (HE), with oxidation products synthesized by many plant and animal species, degrade slowly since many of the derived compounds are persistent. This increases the status of heptachlor as a hazardous pollutant. In the present experimental study we exposed specimens of Rana kl. esculenta, from the tadpole stage through to their complete metamorphosis, to three different concentrations of heptachlor (4, 40 and 400 ppb). Mortality and HE bioaccumulation were evaluated on all the experimental groups. Since amphibian integument directly interacts with the environmental constituents (water, air and soil), we investigated the toxic effects on the ventral epidermis of both tadpole and adult samples by employing such histo-cytopathological biomarkers as ultrastructural morphology, certain enzyme activities (acid and alkaline phosphatases, AcPase, and AlkPase; succinic dehydrogenase, SDH; alpha-naphtyl butyrate esterase, ANBE; nitric oxide synthase/NADPH diaphorase, NOS/NADPHd). Also, the levels of reactive oxygen species (ROS) in the different conditions were evaluated. The results obtained were of ecological relevance, in particular as regards the effects of this environmental toxicant on the samples of tadpole epidermis. Severe morphological alterations were observed in the larval epidermal cells (apical and skein cells), whereas the cell epidermis (keratinocytes and mitochondria-rich cells) of the adult survivors showed changes in enzyme activities, particularly those involved in the protective response to xenobiotic injury. In general, morpho-histochemical studies, analysis of HE bioaccumulation and mortality showed a relation to the H doses employed.
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PMID:Exposure to heptachlor: evaluation of the effects on the larval and adult epidermis of Rana kl. esculenta. 1880 86

Brain-derived neurotrophic factor (BDNF) deficiency has been implicated in pathogenesis of Huntington's disease (HD). 3-Nitropropionic acid (3-NP), an irreversible mitochondrial complex II inhibitor, has been commonly used as a pharmacological model recapitulating HD phenotypes in rodents and nonhuman primates. Herein we test whether BDNF may exert neuroprotective effects against mitochondrial dysfunction caused by 3-NP in primary culture of fetal rat cortical neurons. Preconditioning of neuronal cells with BDNF (100 ng/ml for 8h) attenuated 3-NP toxicity (2.5 mM for additional 24h) based on Hoechst and propidium iodide (PI) staining. BDNF effects can be inhibited by the nitric oxide synthase (NOS) inhibitor L-nitroarginine methylester (L-NAME, 100 microM), the cGMP-dependent protein kinase (PKG) inhibitor KT5823 (2 microM), the thioredoxin reductase inhibitor 1-chloro-2,4-dinitrobenzene (DNCB, 5 microM), and a membrane-permeable Bcl-2 inhibitor (12.5 microM). 8-Br-cGMP is a cGMP analogue capable of activating PKG independent of NO. Exogenous application of 8-Br-cGMP (3-30 microM) and purified thioredoxin (3-5 microM) partially mimicked BDNF effects in conferring 3-NP resistance to cortical cells. These results, together with our previous report showing NO donor S-nitrosoglutathione (GSNO)-mediated neuroprotective effects against 3-NP toxicity, suggest that BDNF may protect neurons from mitochondrial dysfunction at least partly via activation of the signaling cascades involving NOS/NO, PKG, thioredoxin and Bcl-2.
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PMID:Protective effects of brain-derived neurotrophic factor against neurotoxicity of 3-nitropropionic acid in rat cortical neurons. 1942 12


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