Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress because of an excessive production of superoxide anion (O2*-) is associated with hypertension. The present study evaluated the hypothesis that in the rostral ventrolateral medulla (RVLM), where the premotor neurons for the maintenance of vascular vasomotor activity are located, increased O2*- contributes to hypertension in spontaneously hypertensive rats (SHR) by modulating the cardiovascular depressive actions of nitric oxide (NO). Compared with normotensive Wistar-Kyoto (WKY) rats, SHR manifested significantly increased basal O2*- production, along with reduced manganese superoxide dismutase (MnSOD) expression and activity, in the RVLM. The magnitude of hypotension, bradycardia, or suppression of sympathetic neurogenic vasomotor tone elicited by microinjection bilaterally into the RVLM of a membrane-permeable SOD mimetic, Mn(III)-tetrakis-(4-benzoic acid) porphyrin (MnTBAP), was also significantly larger in SHR. Transfection bilaterally into the RVLM of adenoviral vectors encoding endothelial nitric oxide synthase resulted in suppression of arterial pressure, heart rate, and sympathetic neurogenic vasomotor tone in both WKY rats and SHR. Microinjection of MnTBAP into the RVLM of SHR further normalized those cardiovascular parameters to the levels of WKY rats. We conclude that an elevated level of O2*- in the RVLM is associated with hypertension in SHR. More importantly, this elevated O2*- may contribute to hypertension by reducing the NO-promoted cardiovascular depression.
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PMID:Increased superoxide anion in rostral ventrolateral medulla contributes to hypertension in spontaneously hypertensive rats via interactions with nitric oxide. 1564 47

Effect of hexavalent chromium (Cr6+) was seen on Brassica juncea cv. Pusa Jaikisan grown for 15 days in hydroponic culture supplemented with 0.2, 2 and 20 microM Cr. The inhibitory response of Cr6+ on growth of B. juncea was concentration and time dependent. The stimulation of plant growth, observed in response to exposure to 0.2 microM Cr6+, during initial 5 days was reversed on prolonged treatment and at higher Cr6+ concentrations (2 and 20 microM Cr6+). Despite reduction in growth, chlorophyll content increased substantially on 15 days exposure to 20 microM Cr6+. Significant increases in lipid peroxidation and tissue concentration of H2O2 occurred in plants exposed to 2 and 20 microM Cr6+. Effect of Cr6+ on antioxidative enzymes in roots and leaves was differential. SOD and CAT activities at lower levels of Cr6+ supply remained higher all through the treatment. While APX was very susceptible to excess Cr6+, GR and GST increased at elevated levels of Cr6+. The results suggested Cr6+ induced depression in plant growth of B. juncea to be a function of increased cellular accumulation of Cr despite increase in the activities of some of the antioxidative enzymes.
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PMID:Antioxidative responses in relation to growth of mustard (Brassica juncea cv. Pusa Jaikisan) plants exposed to hexavalent chromium. 1615 68

A study is presented of the effect of the cAMP cascade on oxygen metabolism in mammalian cell cultures. Serum-starvation of the cell cultures resulted in depression of the forward NADH-ubiquinone oxidoreductase activity of complex I, decreased content of glutathione, and enhancement of the cellular level of H2O2. Depressed transcription of cytosolic Cu/Zn-SOD 1, mitochondrial glutathione peroxidase and catalase was also observed. Activation of the cAMP cascade reversed the depression of the activity of complex I and the accumulation of H2O2. The effect of cAMP involved the cAMP-dependent protein kinase.
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PMID:Regulation by the cAMP cascade of oxygen free radical balance in mammalian cells. 1667 93

In the present study, the role of pentacyclic triterpenes, lupeol and its ester lupeol linoleate, was studied in relation to hepatic oxidative abnormalities and lipoprotein peroxidation in hypercholesterolemic rats. Hypercholesterolemia was induced in male Wistar rats by feeding them with high cholesterol diet (4% cholesterol + 1% cholic acid; HCD) for 30 days. Pentacyclic triterpenes, lupeol and lupeol linoleate were supplemented (50 mg/kg body wt/day) during the last 15 days. After the experimental period, there was a significant depression in hepatic activities of antioxidant enzymes, SOD (38.39%), CAT (25.03%) and GPx (30.26%) along with a marked fall in the levels of non-enzymic antioxidant molecules GSH (31.39%), vitamin C (46.07%) and vitamin E (42.28%), with a concomitant increase (p<0.001) in lipid peroxidation and in the activities of serum alkaline phosphatase, lactate dehydrogenase and aminotransferases when compared to controls. Treatment with triterpenes decreased lipid peroxidation and reverted the activities of antioxidants (p<0.001 and p<0.01) and marker enzymes to near control. Histopathological findings further confirmed the hepatoprotective nature of triterpenes by showing the normal architecture in treated rats, as against the fatty cellular changes in HCD fed rats. Further, the susceptibility of apo-B containing lipoprotein to oxidation by copper and Fenton's reagent was increased in in vitro condition in HCD fed rats, whereas the lipoproteins were less susceptible to oxidation in triterpenes treated animals. Therefore, it may be concluded that lupeol and its ester afford protection against the hepatic abnormalities and lipoprotein peroxidation in hypercholesterolemic rats.
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PMID:Mitigating role of lupeol and lupeol linoleate on hepatic lipemic-oxidative injury and lipoprotein peroxidation in experimental hypercholesterolemia. 1693 29

Serotonin 5-HT(2C) receptors represent targets for therapeutics aimed at treating anxiety, depression, schizophrenia, and obesity. Previously, we demonstrated that 5-HT(2C) receptors function as homodimers. Herein, we investigated the effect of agonist and inverse agonist treatment on the homodimer status of two naturally occurring 5-HT(2C) receptor isoforms, one without basal activity (VGV) and one with constitutive activity (INI) with respect to Galpha(q) signaling. Cyan- and yellow-fluorescent proteins were used to monitor VGV and INI homodimer formation by western blot, and in living cells using bioluminescence and fluorescence resonance energy transfer (BRET and FRET). Western blots of solubilized membrane proteins revealed equal proportions of homodimeric receptor species from HEK293 cells transfected with either the VGV or INI isoform in the absence and presence of 5-HT. BRET ratios measured in HEK293 cells transfected with the VGV or INI isoform were the same and were not modulated by 5-HT. Similarly, FRET efficiencies were the same regardless of whether measured in cells expressing the VGV or INI isoform in the absence or presence of 5-HT or clozapine. The results indicate that serotonin 5-HT(2C) receptors form homodimers regardless of whether they are in an inactive or active conformation and are not regulated by drug treatment.
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PMID:Serotonin 5-HT(2C) receptor homodimerization is not regulated by agonist or inverse agonist treatment. 1750 8

Thyroid hormones are associated with the oxidative and antioxidative status of the organism. Depression of metabolism by hypothyroidism has been reported to decrease oxidant production and thus protect tissues against oxidant damage. The purpose of the present study was to investigate Zn and Cu levels in MMI-induced hypothyroidism and to show whether there is a connection between these trace elements and the oxidant-antioxidant status in experimental hypothyroidism. 3-Nitrotyrosine was measured as a marker of nitro-oxidative stress. In order to examine the antioxidant status of MMI-induced hypothyroidism in rats, GSH and SOD levels were determined as well. Significantly decreased 3-nitrotyrosine, Cu and Zn levels were observed in our experimental model when compared with the controls. On the other hand, GSH and SOD levels remained constant. It may be suggested that Cu and Zn serve as antioxidant molecules and exert their effects in an indirect manner to reduce oxidative stress in experimental hypothyroidism.
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PMID:Investigation of zinc and copper levels in methimazole-induced hypothyroidism: relation with the oxidant-antioxidant status. 1797 9

Skeletal muscle often shows a delayed force recovery after fatiguing stimulation, especially at low stimulation frequencies. In this study we focus on the role of reactive oxygen species (ROS) in this fatigue-induced prolonged low-frequency force depression. Intact, single muscle fibres were dissected from flexor digitorum brevis (FDB) muscles of rats and wild-type and superoxide dismutase 2 (SOD2) overexpressing mice. Force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)) were measured. Fibres were stimulated at different frequencies before and 30 min after fatigue induced by repeated tetani. The results show a marked force decrease at low stimulation frequencies 30 min after fatiguing stimulation in all fibres. This decrease was associated with reduced tetanic [Ca(2+)](i) in wild-type mouse fibres, whereas rat fibres and mouse SOD2 overexpressing fibres instead displayed a decreased myofibrillar Ca(2+) sensitivity. The SOD activity was approximately 50% lower in wild-type mouse than in rat FDB muscles. Myoplasmic ROS increased during repeated tetanic stimulation in rat fibres but not in wild-type mouse fibres. The decreased Ca(2+) sensitivity in rat fibres could be partially reversed by application of the reducing agent dithiothreitol, whereas the decrease in tetanic [Ca(2+)](i) in wild-type mouse fibres was not affected by dithiothreitol or the antioxidant N-acetylcysteine. In conclusion, we describe two different causes of fatigue-induced prolonged low-frequency force depression, which correlate to differences in SOD activity and ROS metabolism. These findings may have clinical implications since ROS-mediated impairments in myofibrillar function can be counteracted by reductants and antioxidants, whereas changes in SR Ca(2+) handling appear more resistant to interventions.
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PMID:Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice. 1800 75

Metalloenzymes catalyze some of the most demanding reactions in biochemistry, thereby enabling organisms to extract energy from redox reactions and utilize inorganic starting materials such as N 2 and CH 4. Bound metal ions bring to enzymes greater chemical versatility and reactivity than would be possible from amino acids alone. However the host proteins must control this broad reactivity, activating the metal for the intended reaction while excluding the rest of its chemical repertoire. To this end, metalloproteins must control the metal ion reduction midpoint potential ( E m), because the E m determines what redox reactions are possible. We have documented potent redox tuning in Fe- and Mn-containing superoxide dismutases (FeSODs and MnSODs), and manipulated it to generate FeSOD variants with E ms spanning 900 mV (21 kcal/mol or 87 kJ/mol) with retention of overall structure. This achievement demonstrates possibilities and strategies with great promise for efforts to design or modify catalytic metal sites. FeSODs and MnSODs oxidize and reduce superoxide in alternating reactions that are coupled to proton transfer, wherein the metal site is believed to cycle between M3+ x OH- and M2+ x OH2 (M = Fe or Mn). Thus the E m reflects the ease both of reducing the metal ion and of protonating the coordinated solvent molecule. Moreover similar E ms are achieved by Fe-specific and Mn-specific SODs despite the very different intrinsic E(m)s of high-spin Fe3+/2+ and Mn3+/2+. We provide evidence that E(m) depression by some 300 mV can be achieved via a key enforced H-bond that appears able to disfavor proton acquisition by coordinated solvent. Based on 15N-nuclear magnetic resonance (NMR), stronger H-bond donation to coordinated solvent can explain the greater redox depression achieved by the Mn-specific SOD protein compared with the Fe-specific protein. Furthermore, by manipulating the strength and polarity of this one H-bond, with comparatively minor perturbation to active site atomic and electronic structure, we succeeded in raising the E m of FeSOD by more than 660 mV, apparently by a combination of promoting protonation of coordinated solvent and providing an energetically favorable source of a redox-coupled proton. These studies have combined the use of electron paramagnetic resonance (EPR), NMR, magnetic circular dichroism (MCD), and optical spectrophotometry to characterize the electronic structures of the various metal sites, with complementary density functional theoretical (DFT) calculations, NMR spectroscopy, and X-ray crystallography to define the protein structures and protonation states. Overall, we have generated structurally homologous Fe sites that span some 900 mV, and have demonstrated the enormous redox tuning accessible via the energies associated with proton transfer coupled to electron transfer. In this regard, we note the possible significance of coordinated solvent molecules in numerous biological redox-active metal sites besides that of SOD.
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PMID:Redox tuning over almost 1 V in a structurally conserved active site: lessons from Fe-containing superoxide dismutase. 1837 53

Curcumin, a yellow pigment present in the Indian spice turmeric (associated with curry powder), has been linked with suppression of inflammation; angiogenesis; tumorigenesis; diabetes; diseases of the cardiovascular, pulmonary, and neurological systems, of skin, and of liver; loss of bone and muscle; depression; chronic fatigue; and neuropathic pain. The utility of curcumin is limited by its color, lack of water solubility, and relatively low in vivo bioavailability. Because of the multiple therapeutic activities attributed to curcumin, however, there is an intense search for a "super curcumin" without these problems. Multiple approaches are being sought to overcome these limitations. These include discovery of natural curcumin analogues from turmeric; discovery of natural curcumin analogues made by Mother Nature; synthesis of "man-made" curcumin analogues; reformulation of curcumin with various oils and with inhibitors of metabolism (e.g., piperine); development of liposomal and nanoparticle formulations of curcumin; conjugation of curcumin prodrugs; and linking curcumin with polyethylene glycol. Curcumin is a homodimer of feruloylmethane containing a methoxy group and a hydroxyl group, a heptadiene with two Michael acceptors, and an alpha,beta-diketone. Structural homologues involving modification of all these groups are being considered. This review focuses on the status of all these approaches in generating a "super curcumin.".
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PMID:Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. 1877 80

The seeds of Psoralea corylifolia L., an important medicinal herb in Indian and Chinese Pharmacopeia were exposed to gamma rays (2.5, 5, 10, 15 and 20 kGy) from Co(60) source at dose rate of 1.65 kGy h(-1). Enzymatic and non-enzymatic anti-oxidant responses were verified according to the developmental stages and gamma dose applied. Plants grown from seeds exposed to higher gamma doses exhibit higher activity of the antioxidants such as [Ascorbate peroxidase (APX, 1.11.1.1), superoxide dismutase (SOD, 1.15.1.1), glutathione reductase (GR, 1.6.4.2) and MDA content till flowering and declined thereafter. In contrast, CAT (1.11.1.6) activity declined in dose and age dependent manner. The correlation of gamma dose applied and oxidative stress was inferred from the increased enzymes activities and depression in total glutathione pool in seedlings developed from irradiated seeds. Nevertheless, the maintenance of high anti-oxidant capacity, psoralen accumulation seems to be an important strategy during acclimation of P. corylifolia to gamma radiation stress. Pronounced accumulation of psoralen following 15 and 20 kGy at post-flowering stage where oxidative stress is triggered modulates lipid peroxidation and proline accumulation. Further, in psoralen producing plants an increase in psoralen content can be used as a biomarker which specifies plant is under stress.
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PMID:Anti-oxidant modulation in response to gamma radiation induced oxidative stress in developing seedlings of Psoralea corylifolia L. 2272 39


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