The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
L T Young - One of the best experts on this subject based on the ideXlab platform.
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decreased mrna expression of uncoupling protein 2 a mitochondrial proton transporter in post mortem prefrontal cortex from patients with bipolar disorder and schizophrenia
Neuroscience Letters, 2011Co-Authors: Alexandre Duarte Gigante, Ana Cristina Andreazza, Beny Lafer, Lakshmi N Yatham, Clare L Beasley, L T YoungAbstract:Although the neurobiological basis of bipolar disorder (BD) remains unknown, mitochondrial dysfunction, oxidative stress and oxidative cell damage have been identified in this disease. Uncoupling proteins (UCP) are proton carriers located in the inner membrane of the mitochondria involved in controlling the production of mitochondrial reactive oxygen species (ROS). Therefore, in this study we wished to investigate the involvement of UCP in BD. We analyzed the RNA and protein levels of UCP2 in the dorsolateral prefrontal cortex (DLPFC) of subjects with BD and schizophrenia (SCZ) and assessed the potential relationship between the antioxidant superoxide dismutase (SOD1 and SOD2) and UCP2 in the same region. Our results showed a downregulation of UCP2 mRNA levels in the DLPFC of subjects with BD and SCZ. There were no differences in UCP2 protein, SOD1 and SOD2 levels between patients and controls. Although more studies are necessary, our results suggest that UCP2 is not been used as a compensatory mechanism to oppose the higher levels of oxidative stress found in BD and SCZ.
Jing Yang - One of the best experts on this subject based on the ideXlab platform.
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induction of time and dose dependent oxidative stress of triazophos to brain and liver in zebrafish danio rerio
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2020Co-Authors: Guihua Wang, Manni Wu, Dongmei Xiong, Lixin Wang, Jing YangAbstract:Abstract Extensive use of triazophos for the chemical control of pests in agriculture or aquaculture might strongly disturb the aquatic environment due to residue accumulation through various routes like surface run-off, spray-drift and effluent from factories, which have potential negative effects to non-target aquatic organisms. Previous studies have documented the antioxidative effects of triazophos to mammals, however, the oxidative toxicity of triazophos to fish has not been adequately studied to date. Thus, an acute exposure (96 h) to triazophos at different concentrations of 0.06, 0.3 and 1.5 mg/L (corresponding to 1/50th, 1/10th and 1/2th of 96 h-LC50, respectively), was conducted to investigate the triazophos-induced oxidative stress in adult zebrafish (Danio rerio). The results showed that the time- and dose-dependent induction of oxidative stress except for the ROS level in liver after 24 and 48 h exposure, as indicated by increased reactive oxygen species (ROS), malondialdehyde (MDA) level and a compromised antioxidant defense system, including increased superoxide dismutase (SOD) activity, catalase (CAT) activity, glutathione (GSH) content as well as the increased at first and decreased afterwards genes expression (Sod1, SOD2, Cat and Gpx) in brain. Simultaneously, ROS and MDA showed an increased trend, SOD activity, CAT activity and GSH content showed a trend of increasing at 24 h and decreasing at 48 h, and then increasing at 96 h and Sod1, SOD2, Cat and Gpx gene showed decreasing at first and then increasing in liver tissue. The present study concluded that the damage of the antioxidant system by triazophos induced oxidative stress in the brain and liver of zebrafish with concomitant lipid peroxidation, which is an important mechanism underlying the triazophos-induced acute toxicity.
John P Phillips - One of the best experts on this subject based on the ideXlab platform.
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compartment specific protection of iron sulfur proteins by superoxide dismutase
Journal of Biological Chemistry, 2003Co-Authors: Fanis Missirlis, Tracey A Rouault, Kim Kirby, Arthur J Hilliker, John P PhillipsAbstract:Iron and oxygen are essential but potentially toxic constituents of most organisms, and their transport is meticulously regulated both at the cellular and systemic levels. Compartmentalization may be a homeostatic mechanism for isolating these biological reactants in cells. To investigate this hypothesis, we have undertaken a genetic analysis of the interaction between iron and oxygen metabolism in Drosophila. We show that Drosophila iron regulatory protein-1 (IRP1) registers cytosolic iron and oxidative stress through its labile iron sulfur cluster by switching between cytosolic aconitase and RNA-binding functions. IRP1 is strongly activated by silencing and genetic mutation of the cytosolic superoxide dismutase (Sod1), but is unaffected by silencing of mitochondrial SOD2. Conversely, mitochondrial aconitase activity is relatively insensitive to loss of Sod1 function, but drops dramatically if SOD2 activity is impaired. This strongly suggests that the mitochondrial boundary limits the range of superoxide reactivity in vivo. We also find that exposure of adults to paraquat converts cytosolic aconitase to IRP1 but has no affect on mitochondrial aconitase, indicating that paraquat generates superoxide in the cytosol but not in mitochondria. Accordingly, we find that transgene-mediated overexpression of SOD2 neither enhances paraquat resistance in Sod1+ flies nor compensates for lack of SOD1 activity in Sod1-null mutants. We conclude that in vivo, superoxide is confined to the subcellular compartment in which it is formed, and that the mitochondrial and cytosolic SODs provide independent protection to compartment-specific protein iron-sulfur clusters against attack by superoxide generated under oxidative stress within those compartments.
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rna interference mediated silencing of SOD2 in drosophila leads to early adult onset mortality and elevated endogenous oxidative stress
Proceedings of the National Academy of Sciences of the United States of America, 2002Co-Authors: Kim Kirby, Arthur J Hilliker, John P PhillipsAbstract:Oxidative stress has been widely implicated as an important factor in the aging process. Because mitochondrial respiration is the principal source of reactive oxygen within cells, the mitochondrially localized superoxide dismutase (SOD) 2 is thought to play an important front-line defensive role against aging-related oxidative stress. Although genetic studies with mutants deficient in SOD1, the predominantly cytosolic isoform of SOD, have been instrumental in elucidating the role of reactive oxygen metabolism in aging in Drosophila, the lack of available mutations in the SOD2 gene has hampered an equivalent analysis of the participation of this important antioxidant enzyme in the Drosophila aging model. Here we report that ablation of mitochondrial SOD2 through expression of a GAL4-regulated, inverted-repeat SOD2 RNA-interference transgene in an otherwise normal animal causes increased endogenous oxidative stress, resulting in loss of essential enzymatic components of the mitochondrial respiratory chain and the tricarboxylic acid cycle, enhances sensitivity to applied oxidative stress, and causes early-onset mortality in young adults. In sharp contrast, ablation of SOD2 has no overt effect on the development of larvae and pupae, which may reflect a fundamental transition in oxygen utilization and/or reactive oxygen metabolism that occurs during metamorphosis from larval to adult life.
Brendan J. Waddell - One of the best experts on this subject based on the ideXlab platform.
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Antioxidant Defenses in the Rat Placenta in Late Gestation: Increased Labyrinthine Expression of Superoxide Dismutases, Glutathione Peroxidase 3, and Uncoupling Protein 2
Biology of Reproduction, 2010Co-Authors: Megan L. Jones, Peter J. Mark, Jessica L. Lewis, Trevor A. Mori, Jeffery A. Keelan, Brendan J. WaddellAbstract:Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR). Oxidative stress occurs when accumulation of reactive oxygen species (ROS) damages DNA, proteins and lipids, an outcome that is limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) may also limit oxidative stress by reducing ROS production. Here we characterized placental antioxidant defenses during normal gestation and following glucocorticoidinduced IUGR. Placentas were collected on Days 16 and 22 of normal rat pregnancy (term ¼ Day 23) and at Day 22 after dexamethasone treatment from Day 13. Expression of several genes encoding antioxidant enzymes (Sod1, SOD2, Sod3, Cat, Gpx3, Txn1, Txnrd1, Txnrd2 ,a ndTxnrd3 )a ndUcp2 was measured by quantitative RT-PCR in the labyrinth (LZ) and junctional zones (JZ) of the placenta. Expression of Sod1 and Ucp2 mRNAs and the activity of xanthine oxidase, a source of ROS, all increased from Days 16 to 22 in both placental zones, whereas SOD2 and Gpx3 increased only in the rapidly growing LZ. In contrast, Sod3 and Txnrd1 expression fell in the LZ over this period, whereas total superoxide dismutase activity remained stable. Dexamethasone treatment reduced fetalplacental growth and LZ expression of Ucp2 but increased JZ expression of Txn1. Indices of placental oxidative damage (TBARS, F 2 -isoprostanes, and 8-OHdG) did not change with gestational age or dexamethasone, indicative of adequate antioxidant protection. Overall, our data suggest that the rat placenta is protected from oxidative stress by the dynamic zoneand stage-dependent expression of antioxidant defense genes. antioxidant, glucocorticoid, oxidative stress, placenta, pregnancy
Daret K St Clair - One of the best experts on this subject based on the ideXlab platform.
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regulation of superoxide dismutase genes implications in disease
Free Radical Biology and Medicine, 2009Co-Authors: Lu Miao, Daret K St ClairAbstract:Numerous short-lived and highly reactive oxygen species (ROS) such as superoxide (O2(.-)), hydroxyl radical, and hydrogen peroxide are continuously generated in vivo. Depending upon concentration, location, and intracellular conditions, ROS can cause toxicity or act as signaling molecules. The cellular levels of ROS are controlled by antioxidant enzymes and small-molecule antioxidants. As major antioxidant enzymes, superoxide dismutases (SODs), including copper-zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase, and extracellular superoxide dismutase, play a crucial role in scavenging O2(.-). This review focuses on the regulation of the sod genes coding for these enzymes, with an emphasis on the human genes. Current knowledge about sod structure and regulation is summarized and depicted as diagrams. Studies to date on genes coding for Cu/ZnSOD (sod1) are mostly focused on alterations in the coding region and their associations with amyotrophic lateral sclerosis. Evaluation of nucleotide sequences reveals that regulatory elements of the SOD2 gene reside in both the noncoding and the coding region. Changes associated with SOD2 lead to alterations in expression levels as well as protein function. We also discuss the structural basis for the changes in SOD expression associated with pathological conditions and where more work is needed to establish the relationship between SODs and diseases.