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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondria of rapidly developing mungbean seedlings were fractionated into four populations: two density classes, each from a 1500S and a 150S pellet. Each of the four populations exhibited cytochrome c oxidase (COX) activity and contained mitochondrial DNA and cardiolipin; plastid and glyoxysome content were found to be relatively low. Five mitochondrial membrane proteins, COXII/III, ATPase alpha/beta and porin, and a matrix enzyme, manganese superoxide dismutase (MnSOD), were detected by immunoblots in all four populations. Another matrix enzyme, pyruvate dehydrogenase was detected only in the two respiratory-competent 1500S populations. The two 150S populations contained a previously unidentified organelle that lacked demonstrable respiratory capability. This organelle, which we have tentatively referred to as "slow-sedimenting (ss-) mitochondrion", was small in size (below light-optics resolution, 70-300nm, majority < or =200nm) and possessed a peculiar looking boundary membrane, ribosomes, and an occasional prominent electron-dense spot. Characteristically, ss-mitochondria were almost always in contact with a filament-aligned membrane-like structure of varying length. Cristae structure, while undetected in small ss-mitochondria, appeared in larger individuals. Typical mitochondria were found in the denser 1500S population, while the lighter 1500S population consisted of 300-800 nm mitochondria exhibiting a varying degree of size-dependent inner membrane folding. Using electron microscopy (EM) immunolocalization and serial sectioning, we have identified in situ organelles resembling in size and in fine structure the ss-mitochondria, which also exhibit a size-dependent folding of the inner membrane. These results suggest that small ss-mitochondria may undergo a progressive development in situ. Taken together, our findings demonstrate the existence of a pattern of structure-function-coordinated gross heterogeneity among mitochondria. This pattern of mitochondrial heterogeneity, characterized both in isolated mitochondria and in situ, implies that small ss-mitochondria may represent a type of "nascent mitochondria" derived from a yet unidentified mitochondria-propagation mode operating during rapid seedling growth. Mitochondrial division by binary fission, characterized by the appearance of dumbbell-shaped intermediates, was also detected.
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PMID:Population heterogeneity of higher-plant mitochondria in structure and function. 954 77

Hypoxia has been shown to cause lung edema and impair lung edema clearance. In the present study, we exposed isolated rat lungs to pO(2) = 40 mm Hg for 60 min or rats to 8% O(2) for up to 24 h and then measured changes in alveolar fluid reabsorption (AFR) and Na,K-ATPase function. Low levels of oxygen severely impaired AFR in both ex vivo and in vivo models. The decrease in AFR was associated with a decrease in Na,K-ATPase activity and protein abundance in the basolateral membranes from peripheral lung tissue of hypoxic rats. Beta-adrenergic agonists restored AFR in rats exposed to 8% O(2) (from 0.02 +/- 0.07 ml/h to 0.59 +/- 0.03 ml/h), which was associated with parallel increases in Na,K-ATPase protein abundance in the basolateral membrane. Hypoxia is associated with increased production of reactive oxygen species. Therefore, we examined whether overexpression of SOD2, manganese superoxide dismutase, would prevent the hypoxia-mediated decrease in AFR. Spontaneously breathing rats were infected with a replication-deficient human type 5 adenovirus containing cDNA for SOD2. An otherwise identical virus that contained no cDNA was used as a control (Adnull). Hypoxic Adnull rats had decreased rates of AFR (0.12 +/- 0.1 ml/h) as compared with hypoxic AdSOD2 and normoxic control rats (0.47 +/- 0.04 ml/h and 0.49 +/- 0.02 ml/h, respectively), with parallel changes in Na,K-ATPase.
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PMID:Beta-adrenergic receptor stimulation and adenoviral overexpression of superoxide dismutase prevent the hypoxia-mediated decrease in Na,K-ATPase and alveolar fluid reabsorption. 1663 55

Renal ischemia/reperfusion (I/R) injury often occurs as a result of vascular surgery, organ procurement, or transplantation. We previously showed that renal I/R results in ATP depletion, oxidant production, and manganese superoxide dismutase (MnSOD) inactivation. There have been several reports that overexpression of MnSOD protects tissues/organs from I/R-related damage, thus a loss of MnSOD activity during I/R likely contributes to tissue injury. The present study examined the therapeutic benefit of a catalytic antioxidant, Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)), using the rat renal I/R model. This was the first study to examine the effects of MnTnHex-2-PyP(5+) in an animal model of oxidative stress injury. Our results showed that porphyrin pretreatment of rats for 24 h protected against ATP depletion, MnSOD inactivation, nitrotyrosine formation, and renal dysfunction. The dose (50 microg/kg) used in this study is lower than doses of various types of antioxidants commonly used in animal models of oxidative stress injuries. In addition, using novel proteomic techniques, we identified the ATP synthase-beta subunit as a key protein induced by MnTnHex-2-PyP(5+) treatment alone and complex V (ATP synthase) as a target of injury during renal I/R. These results showed that MnTnHex-2-PyP(5+) protected against renal I/R injury via induction of key mitochondrial proteins that may be capable of blunting oxidative injury.
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PMID:Manganese porphyrin reduces renal injury and mitochondrial damage during ischemia/reperfusion. 1744 4

Early Alzheimer's disease (EAD) is the intermediary stage between mild cognitive impairment (MCI) and late-stage Alzheimer's disease (AD). The symptoms of EAD mirror the disease advancement between the two phases. Dementia, memory deficits, and cognitive decline are more pronounced as the disease progresses. Oxidative stress in brain is reported in MCI and AD, including lipid peroxidation indexed by protein-bound 4-hydroxy-2-nonenal (HNE). There are limited data regarding the proteomics analysis of brain from subjects with EAD and even less concerning the possible relationship of EAD HNE-modified brain proteins with HNE-modified proteins in MCI and AD. Proteomics was utilized to investigate excessively HNE-bound brain proteins in EAD compared to those in control. These new results provide potentially valuable insight into connecting HNE-bound brain proteins in EAD to those previously identified in MCI and AD, since EAD is a transitional stage between MCI and late-stage AD. In total, six proteins were found to be excessively covalently bound by HNE in EAD inferior parietal lobule (IPL) compared to age-related control brain. These proteins play roles in antioxidant defense (manganese superoxide dismutase), neuronal communication and neurite outgrowth (dihydropyriminidase-related protein 2), and energy metabolism (alpha-enolase, malate dehydrogenase, triosephosphate isomerase, and F1 ATPase, alpha subunit). This study shows that there is an overlap of brain proteins in EAD with previously identified oxidatively modified proteins in MCI and late-stage AD. The results are consistent with the hypothesis that oxidative stress, in particular lipid peroxidation, is an early event in the progression of AD, and is the first to identify in EAD identical brain proteins previously identified as HNE-modified in MCI and late-state AD.
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PMID:Proteomic identification of HNE-bound proteins in early Alzheimer disease: Insights into the role of lipid peroxidation in the progression of AD. 1937 91

Alcohol consumption increases reactive oxygen species (ROS) formation, which can damage mitochondrial DNA (mtDNA) and alter mitochondrial function. To test whether manganese superoxide dismutase (MnSOD) modulates acute alcohol-induced mitochondrial alterations, transgenic MnSOD-overexpressing (MnSOD(+++)) mice, heterozygous knockout (MnSOD(+/-)) mice, and wild-type (WT) littermates were sacrificed 2 or 24 h after intragastric ethanol administration (5 g/kg). Alcohol administration further increased MnSOD activity in MnSOD(+++) mice, but further decreased it in MnSOD(+/-) mice. In WT mice, alcohol administration transiently increased mitochondrial ROS formation, decreased mitochondrial glutathione, depleted and damaged mtDNA, and decreased complex I and V activities; alcohol durably increased inducible nitric-oxide synthase (NOS) expression, plasma nitrites/nitrates, and the nitration of tyrosine residues in complex V proteins. These effects were prevented in MnSOD(+++) mice and prolonged in MnSOD(+/-) mice. In alcoholized WT or MnSOD(+/-) mice, mtDNA depletion and the nitration of tyrosine residues in complex I and V proteins were prevented or attenuated by cotreatment with tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), a superoxide scavenger; N(omega)-nitro-l-arginine methyl ester and N-[3-(aminomethyl)benzyl]acetamidine (1,400W), two NOS inhibitors; or uric acid, a peroxynitrite scavenger. In conclusion, MnSOD overexpression prevents, and MnSOD deficiency prolongs, mtDNA depletion after an acute alcohol binge in mice. The protective effects of MnSOD, tempol, NOS inhibitors, and uric acid point out a role of the superoxide anion reacting with NO to form mtDNA-damaging peroxynitrite.
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PMID:Hepatic mitochondrial DNA depletion after an alcohol binge in mice: probable role of peroxynitrite and modulation by manganese superoxide dismutase. 2001 22

Feeding Wistar rats a high calorie "Western" diet (45% fat) for up to 48 weeks induces obesity and cardiac dysfunction, while a high fat diet (60% fat) induces obesity only. Here we investigated the molecular "footprints" of the two forms of diet-induced obesity in the heart. In rats fed Western diet for a long term, cardiac mRNA transcript levels of malic enzyme were decreased (-72%, P < 0.05), suggesting impaired anaplerotic flux of the Krebs cycle (KC) and mitochondrial dysfunction. In addition, there was a marked decrease in the expression of the transcription factor MEF2C (myocyte enhancer factor 2C) and its target gene SERCA2a (sarco-endo-plasmic reticulum Ca(2+)-ATPase). Oxidative stress was reflected in reduced transcript levels of manganese superoxide dismutase, glutathione peroxidase 1, and increased protein levels of mitochondrial transcription factor A, suggesting compensatory mitochondrial biogenesis in the face of increased mitochondrial damage. Oxidant injury was accompanied by increased protein glycosylation, increased transcript levels of glutamine fructose 6-phosphate amidotransferase 2, and decreased protein levels of acetyl Co-A carboxylase. Lastly, apoptosis was evident by TUNEL positivity and elevated mRNA transcript levels and activity of caspase 3. Consistent with these results, protein levels of Bcl2 were markedly reduced. We conclude that inadequate supplementation of KC intermediates due to reduced levels of malic enzyme, downregulation of MEF2C and its target gene SERCA2a, oxidative stress, and programmed cell death are all potential contributors to contractile dysfunction of the heart.
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PMID:Obesogenic high fat western diet induces oxidative stress and apoptosis in rat heart. 2067 34

Both acute and chronic alcohol consumption increase reactive oxygen species (ROS) formation and lipid peroxidation, whose products damage hepatic mitochondrial DNA (mtDNA). To test whether manganese superoxide dismutase (MnSOD) overexpression modulates acute and chronic alcohol-induced mtDNA lesions, transgenic MnSOD-overexpressing (TgMnSOD(+++)) mice and wild-type (WT) mice were treated by alcohol, either chronically (7 weeks in drinking water) or acutely (single intragastric dose of 5 g/kg). Acute alcohol administration increased mitochondrial ROS formation, decreased mitochondrial glutathione, depleted and damaged mtDNA, durably increased inducible nitric oxide synthase (NOS) expression, plasma nitrites/nitrates and the nitration of tyrosine residues in complex V proteins and decreased complex V activity in WT mice. These effects were prevented in TgMnSOD(+++) mice. In acutely alcoholized WT mice, mtDNA depletion was prevented by tempol, a superoxide scavenger, L-NAME and 1400W, two NOS inhibitors, or uric acid, a peroxynitrite scavenger. In contrast, chronic alcohol consumption decreased cytosolic glutathione and increased hepatic iron, lipid peroxidation products and respiratory complex I protein carbonyls only in ethanol-treated TgMnSOD(+++) mice but not in WT mice. In chronic ethanol-fed TgMnSOD(+++) mice, but not WT mice, mtDNA was damaged and depleted, and the iron chelator, deferoxamine (DFO), prevented this effect. In conclusion, MnSOD overexpression prevents mtDNA depletion after an acute alcohol binge but aggravates this effect after prolonged alcohol consumption, which selectively triggers iron accumulation in TgMnSOD(+++) mice but not in WT mice. In the model of acute alcohol binge, the protective effects of MnSOD, tempol, NOS inhibitors and uric acid suggested a role of the superoxide anion reacting with NO to form mtDNA-damaging peroxynitrite. In the model of prolonged ethanol consumption, the protective effects of DFO suggested the role of iron reacting with hydrogen peroxide to form mtDNA-damaging hydroxyl radical.
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PMID:MnSOD overexpression prevents liver mitochondrial DNA depletion after an alcohol binge but worsens this effect after prolonged alcohol consumption in mice. 2152 61

Previous studies investigating cancer cells cultured at acidic pH have shown that the expression level of ~700 genes were more than two-fold higher than those of the cells cultured in alkaline medium at pH 7.5. The aim of the present study was to confirm whether these acidosis-induced genes are expressed in human cancer tissues. Therefore, 7 genes were selected from our previous study, which encoded interleukin 32 (IL-32), lysosomal H⁺ transporting ATPase, V0 subunit d2 (ATP6V0D2), tumor necrosis factor receptor superfamily, member 9 (TNFRSF9), amphiregulin, schwannoma-derived growth factor (AREG), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ErbB3), PRR5-ARHGAP8 (LOC553158) and dimethylglycine dehydrogenase (DMGDH), and their expression was examined in human clinical specimens from patients with cancer. In addition, the expression of the gene encoding manganese superoxide dismutase (MnSOD) was examined. The specimens from patients with colon, stomach and renal cancer showed increased MnSOD, IL-32, and TNFRSF9 transcripts compared to those from non-tumorous regions of the same patients. Notably, an elevated expression of ATP6V0D2 was found in the specimens from patients with stomach cancer, whereas the expression was decreased in those from patients with colon and renal cancer. The expression of LOC553158 was upregulated in colon and stomach cancer specimens. These results indicate that the investigation of gene expression under acidic conditions is useful for the development of novel cancer markers and/or chemotherapeutic targets.
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PMID:Expression of acidosis-dependent genes in human cancer nests. 2527 16

Mitochondrial dysfunction due to oxidative damage is the key feature of several diseases. We have earlier reported mitochondrial damage resulting from the generation of oxidative stress as a major pathophysiological effect of isoproterenol (ISO)-induced myocardial ischemia in rats. That melatonin is an antioxidant that ameliorates oxidative stress in experimental animals as well as in humans is well established. We previously demonstrated that melatonin provides cardioprotection against ISO-induced myocardial injury as a result of its antioxidant properties. The mechanism of ISO-induced cardiac mitochondrial damage and protection by melatonin, however, remains to be elucidated in vitro. In this study, we provide evidence that ISO causes dysfunction of isolated goat heart mitochondria. Incubation of cardiac mitochondria with increasing concentrations of ISO decreased mitochondrial succinate dehydrogenase (SDH) activity, which plays a pivotal role in mitochondrial bioenergetics, as well as altered the activities of other key enzymes of the Kreb's cycle and the respiratory chain. Co-incubation of ISO-challenged mitochondria with melatonin prevented the alterations in enzyme activity. That these changes in mitochondrial energy metabolism were due to the perpetration of oxidative stress by ISO was evident from the increased levels of lipid peroxidation and decreased reduced glutathione/oxidized glutathione ratio. ISO-induced oxidative stress also altered mitochondrial redox potential and brought about changes in the activity of the antioxidant enzymes manganese superoxide dismutase and glutathione peroxidase, eventually leading to alterations in total ATPase activity and membrane potential. Melatonin ameliorated these changes likely through its antioxidant abilities suggesting a possible mechanism of cardioprotection by this indole against ISO-induced myocardial injury.
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PMID:Mechanisms of isoproterenol-induced cardiac mitochondrial damage: protective actions of melatonin. 2565 73

The present study was designed to investigate the potential role of secretory pathway Ca(2+)-ATPase isoform 1(SPCA1) in experimental focal cerebral ischemia-reperfusion injury. Cerebral ischemia-reperfusion was induced by transient middle cerebral artery occlusion (MCAO) for 2h s in Sprague-Dawley rats, and then the expression levels of SPAC1 mRNA and protein were determined. Results showed that SPCA1 level was transiently increased 1 day after reperfusion in peri-infarction area, while markedly increased in infarction core on 3day and 7 day after reperfusion. Then a SPCA1 lentivirus was used to achieve knockdown of SPCA1 gene: Ca(2+) transporting type 2C, member 1 (ATP2C1) gene. It has been observed that SPCA1 knockdown by lentivirus markedly increased cerebral infarction volume in vivo. Meanwhile, SPCA1 knockdown also facilitated per-oxidative production, including nitric oxide (NO) and 3-nitrotyrosine (3-NT) and decreased the expression of total superoxide dismutase (SOD) and manganese superoxide dismutase (MnSOD). Moreover, in vitro study showed that SPCA1 knockdown increased hydrogen peroxide (H2O2)-induced lactate dehydrogenase (LDH) leakage dose-dependently, and elevated caspase3 level in neuro-2a (N2a) cells. In addition, SPCA1 knockdown increased H2O2-induced production of nitric oxide and 3-NT dose-dependently, and reversed the increased activity of total SOD and MnSOD in neuro-2a cells. In conclusion, the present study indicated that SPCA1 could suppress over active Golgi apparatus (GA) stress thus attenuate cerebral ischemia-reperfusion injury.
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PMID:Secretory pathway Ca(2+)-ATPase isoform 1 knockdown promotes Golgi apparatus stress injury in a mouse model of focal cerebral ischemia-reperfusion: In vivo and in vitro study. 2873 34


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