Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravitreal injection of 5 micrograms of Shigella endotoxin, in the rabbit eye, induced an acute inflammatory response which was characterised by conjunctival hyperaemia, limbal and ciliary vascular injection, iritis, aqueous flare, miosis and reduction in intraocular pressure. Iris-ciliary body tissues, from normal and inflamed eyes, were fractionated into subcellular enriched fractions and the activities and distribution of selected enzymes were estimated. Alkaline phosphatase, a plasma membrane-bound enzyme, showed an increase in activity, whereas succinate dehydrogenase and Mn-Superoxide dismutase, both mitochondrial-bound enzymes, exhibited decreased activities. Lysosomal acid phosphatase displayed an increase in free activity and retention of latent activity inside the organelle. No alteration in free activity was shown by acid cathepsin. The cholinesterases did not exhibit any changes in activities nor did the cytosolic enzymes Cu/Zn-superoxide dismutase and lactate dehydrogenase. The decrease activity of the respiratory mitochondrial enzyme succinate dehydrogenase may contribute to the reduction in intraocular pressure, and the ability of the lysosomal organelles to retain their hydrolytic enzymes, ensures recovery of the cell from acute inflammatory attack.
 ...
PMID:Enzymatic activities in the iris-ciliary body of the rabbit eye during experimentally induced acute ocular inflammation. 349 78

An oxygen-induced iron superoxide dismutase was found in the culture fluid of the thermoacidophilic crenarchaeon Sulfolobus solfataricus during growth on glucose-rich media. This protein was also identified as being associated with the cell-surface, with the amount of the released and cell-bound protein fractions depending on the growth phase of the cells. The steady decrease in cell-associated superoxide dismutase during continued growth correlated with the increase of free superoxide dismutase in the medium. Both enzyme fractions were purified to homogeneity and found to be active with different catalytic efficiency, with the released superoxide dismutase showing a fourfold lower specific activity. Characterization in comparison with the cytosolic superoxide dismutase revealed identical N-terminal sequences, electrophoretic mobility, isoelectric point, and molecular mass for all three differently located enzymes. In order to clarify the physiological role of the cell-associated superoxide dismutase, the prevention of cell-bound protein deactivation by oxyradicals was also investigated. Glucose dehydrogenase, which was chosen as a model enzyme, was demonstrated to be located on the cell surface and to be inactivated by potassium superoxide by in vivo assays. The direct protective effect of superoxide dismutase on glucose dehydrogenase was demonstrated by in vitro assays on the free released enzyme. Similarly, the prevention of deactivation by potassium superoxide was also demonstrated for the integral membrane protein succinate dehydrogenase by intact cell assay. Superoxide dismutase added to cells was shown to moderately reduce the critical damaging peroxidation and hence play a major role in maintaining the integrity of the outer cell envelope components.
 ...
PMID:A superoxide dismutase from the archaeon Sulfolobus solfataricus is an extracellular enzyme and prevents the deactivation by superoxide of cell-bound proteins. 1060 72

The oxidative stress possibly resulting from an inherited respiratory chain (RC) deficiency was investigated in a series of human cultured skin fibroblasts presenting either ubiquinone depletion or isolated defect of the various RC complexes. Taken as an index for superoxide overproduction, a significant induction of superoxide dismutase activity was observed in complex V-deficient fibroblasts harboring the NARP-mutation in the ATPase 6 gene. Superoxide dismutase induction was also noticed, albeit to a lesser extent, in complex II-deficient fibroblasts with a mutation in the nuclear gene encoding the flavoprotein subunit of the succinate dehydrogenase. No sign of oxidative stress could be found in ubiquinone-depleted fibroblasts. In all cases but complex IV-defect, increased oxidative stress was associated with increased cell death. In glucose-rich medium, apoptosis appeared as the main cell death process associated with all types of RC defect. However, similar to the great variations in oxidative stress associated with the various types of RC defect, we found that apoptotic features differed noticeably between defects. No indication of increased cell death was found in ubiquinone-depleted fibroblasts.
 ...
PMID:Coenzyme Q10 depletion is comparatively less detrimental to human cultured skin fibroblasts than respiratory chain complex deficiencies. 1206

We investigated the effect of diazoxide on neuronal survival in primary cultures of rat cortical neurons against oxygen-glucose deprivation (OGD). Diazoxide pre-treatment induced delayed pre-conditioning and almost entirely attenuated the OGD-induced neuronal death. Diazoxide inhibited succinate dehydrogenase and induced mitochondrial depolarization, free radical production and protein kinase C activation. The putative mitochondrial ATP-sensitive potassium channel blocker 5-hydroxydecanoate abolished the protective effect of diazoxide while the non-selective KATP channel blocker glibenclamide did not. The non-selective KATP channel openers nicorandil and cromakalim did not improve viability. Superoxide dismutase mimetic, M40401, or protein kinase C inhibitor, chelerythrine, prevented the neuroprotective effect of diazoxide. Diazoxide did not increase reduced glutathione and manganese-superoxide dismutase levels but we found significantly higher reduced glutathione levels in diazoxide-pre-conditioned neurons after OGD. In pre-conditioned neurons free radical production was reduced upon glutamate stimulation. The succinate dehydrogenase inhibitor 3-nitropropionic acid also induced pre-conditioning and free radical production in neurons. Here, we provide the first evidence that diazoxide induces delayed pre-conditioning in neurons via acute generation of superoxide anion and activation of protein kinases and subsequent attenuation of oxidant stress following OGD. The succinate dehydrogenase-inhibiting effect of diazoxide is more likely to be involved in this neuroprotection than the opening of mitochondrial ATP-sensitive potassium channels.
 ...
PMID:Diazoxide induces delayed pre-conditioning in cultured rat cortical neurons. 1462 27

Reamberin in a dose of 25 mg/kg (succinate concentration) was injected intravenously for 3 days starting from the 1st hour after skin ischemia modeling. This treatment decreased activities of lactate dehydrogenase, aspartate transaminase, and creatine phosphokinase in skin homogenates by 1.6 times, 19%, and 51.3%, respectively. The index of cytolysis decreased by 18%. Reamberin had an energotropic effect, which manifested in an increase in the total ATP content and concentration of creatine phosphate (by 16 and 10%, respectively). After administration of Reamberin, activity of the succinate-ubiquinone reductase system increased by 17%. Under these conditions succinate dehydrogenase activity exceeded the normal by 21%. Reamberin had no effect on the mitochondrial NADH-ubiquinone reductase system in dermal cells during skin ischemia. Superoxide dismutase activity in the area of necrosis increased to the control level on day 3 of treatment with Reamberin. Activities of catalase and glutathione peroxidase increased by 13 and 19%, respectively. Our results indicate that the course of intravenous treatment with Reamberin for 3 days contributes to an increase in reserve capacities of the antioxidant protection system and produces a protective effect during skin ischemia.
 ...
PMID:Protective effect of reamberin on functional activity of mitochondria during skin ischemia. 1667 75

The hypothesis was tested that endothelin-1 (ET-1)-induced superoxide (O(2)(-)) generation mediates post-ischemic coronary endothelial injury, that ischemic preconditioning (IPC) affords endothelial protection by preventing post-ischemic ET-1, and thus O(2)(-), generation, and that opening of the mitochondrial ATP-dependent potassium channel (mK(ATP)) triggers the mechanism of IPC. Furthermore, the study was aimed at identifying the source of O(2)(-) mediating the endothelial injury. Langendorff-perfused guinea-pig hearts were subjected either to 30 min ischemia/35 min reperfusion (IR) or were preconditioned prior to IR with three cycles of either 5 min ischemia/5 min reperfusion or 5 min infusion/5 min washout of mK(ATP) opener diazoxide (0.5 mM). Coronary flow responses to acetylcholine (ACh) served as a measure of endothelium-dependent vascular function. Myocardial outflow of ET-1 and O(2)(-) and functional recoveries were followed during reperfusion. NADPH oxidase and xanthine oxidase (XO) activities were measured in cardiac homogenates. IR augmented ET-1 and O(2)(-) outflow and impaired ACh response. All these effects were attenuated or prevented by IPC and diazoxide, and 5-hydroxydecanoate (a selective mK(ATP) blocker) abolished the effects of IPC and diazoxide. Superoxide dismutase and tezosentan (a mixed ET-1-receptor antagonist) mimicked the effects of IPC, although they had no effect on the ET-1 generation. IR augmented also the activity of NADPH oxidase and XO. Apocynin treatment, that resulted in NADPH oxidase inhibition, prevented XO activation and O(2)(-) generation in IR hearts. The inhibition of XO, either by allopurinol or feeding the animals with tungsten-enriched chow, prevented post-ischemic O(2)(-) generation, although these interventions had no effect on the NADPH activity. In addition, the post-ischemic activation of NADPH oxidase and XO, and O(2)(-) generation were prevented by IPC, tezosentan, thenoyltrifluoroacetone (mitochondrial complex II inhibitor), and tempol (cell-membrane permeable O(2)(-) scavenger). In guinea-pig heart: (i) ET-1-induced O(2)(-) generation mediates post-ischemic endothelial dysfunction; (ii) IPC and diazoxide afford endothelial protection by attenuating the ET-1, and thus O(2)(-) generation, and the mK(ATP) opening triggers the protection; (iii) the NADPH oxidase maintains the activity of XO, and the XO-derived O(2)(-) mediates the endothelial injury, and (iv) ET-1 and O(2)(-) (probably of mitochondrial origin) are upstream activators of the NADPH oxidase-XO cascade, and IPC prevents the cascade activation and the endothelial dysfunction by preventing the ET-1 generation.
 ...
PMID:Preconditioning protects endothelium by preventing ET-1-induced activation of NADPH oxidase and xanthine oxidase in post-ischemic heart. 1715 94

Earlier studies reported accumulation of mitochondrial DNA mutations in ageing and age-related macular degeneration. To know about the mitochondrial status with age, we examined immunoreactivity (IR) to markers of mitochondria (anti-mitochondrial antibody and voltage-dependent anion channel-1) and complex I-V (that mediate oxidative phosphorylation, OXPHOS) in donor human retinas (age: 19-94years; N=26; right eyes). In all samples, at all ages, IR to anti-mitochondrial antibody and voltage-dependent anion channel-1 was prominent in photoreceptor cells. Between second and seventh decade of life, strong IR to complex I-V was present in photoreceptors over macular to peripheral retina. With progressive ageing, the photoreceptors showed a decrease in complex I-IR (subunit NDUFB4) at eighth decade, and a weak or absence of IR in 10 retinas between ninth and tenth decade. Patchy IR to complex III and complex IV was detected at different ages. IR to ND1 (complex I) and complex II and V remained unaltered with ageing. Nitrosative stress (evaluated by IR to a nitro-tyrosine antibody) was found in photoreceptors. Superoxide dismutase-2 was found upregulated in photoreceptors with ageing. Mitochondrial ultrastructure was examined in two young retinas with intact complex IR and six aged retinas whose counterparts showed weak to absence of IR. Observations revealed irregular, photoreceptor inner segment mitochondria in aged maculae and mid-peripheral retina between eighth and ninth decade; many cones possessed autophagosomes with damaged mitochondria, indicating age-related alterations. A trend in age-dependent reduction of complex I-IR was evident in aged photoreceptors, whereas patchy complex IV-IR (subunits I and II) was age-independent, suggesting that the former is prone to damage with ageing perhaps due to oxidative stress. These changes in OXPHOS system may influence the energy budget of human photoreceptors, affecting their viability.
 ...
PMID:Immunolocalisation pattern of complex I-V in ageing human retina: Correlation with mitochondrial ultrastructure. 2758 Dec 13

Numerous ethnomedicinal uses have been attributed to different parts of Annona senegalensis (ASE), including its uses as food and food additives. The present study investigated toxicological and antioxidant effects of 28 days administration of ethanol extracts of ASE stem bark to Wistar strain albino rats. Acute toxicity test was done to determine lethal dose in Wistar rats while sub-acute toxicity test was conducted on rats divided into four groups (A - control, B - 50 mg/kg, C - 100 mg/kg, D - 150 mg/kg, respectively and treated for 28 days. Oxidative stress markers in liver and kidney as well as hepatic succinate dehydrogenase activity in the mitochondrial and post mitochondrial fractions (PMF) were evaluated. The LD50 value of ASE was > 2,000 mg/kg. White blood cell counts gradually increased, but red blood cell counts and haematocrits level decreased significantly (p < 0.05) by about 50%. Liver enzymes in the serum and mitochondrial succinate dehydrogenase activity increased significantly (p < 0.05). Superoxide dismutase and catalase activities also increased in liver mitochondria and PMF while malondialdehyde (MDA) and reduced glutathione levels increased only in the PMF. Furthermore, only MDA levels increased significantly in the kidney after 28 days extract administration. Histopathological examination showed hepatic necrosis and no obvious signs of nephrotoxicity. Anona senegalensis is relatively safe, but prolonged ingestion could induce oxidative stress and impair ATP synthesis through the modulation of the activity of mitochondrial succinate dehydrogenase.
 ...
PMID:Alterations of Antioxidant Status and Mitochondrial Succinate Dehydrogenase Activity in the Liver of Wistar Strain Albino Rats Treated with by Ethanol Extracts of Annona senegalensis Pers (Annonaceae) Stem Bark. 3076 54