Superoxide dismutase explained

Superoxide dismutase
Ec Number:1.15.1.1
Cas Number:9054-89-1
Go Code:0004784

Superoxide dismutase (SOD,) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide anion radical into normal molecular oxygen (O2) and hydrogen peroxide . Superoxide is produced as a by-product of oxygen metabolism and, if not regulated, causes many types of cell damage.[1] Hydrogen peroxide is also damaging and is degraded by other enzymes such as catalase. Thus, SOD is an important antioxidant defense in nearly all living cells exposed to oxygen. One exception is Lactobacillus plantarum and related lactobacilli, which use intracellular manganese to prevent damage from reactive .[2] [3]

Chemical reaction

SODs catalyze the disproportionation of superoxide:

+ → + In this way, is converted into two less damaging species.

The general form, applicable to all the different metal−coordinated forms of SOD, can be written as follows:

The reactions by which SOD−catalyzed dismutation of superoxide for Cu,Zn SOD can be written as follows:

where M = Cu (n=1); Mn (n=2); Fe (n=2); Ni (n=2) only in prokaryotes.

In a series of such reactions, the oxidation state and the charge of the metal cation oscillates between n and n+1: +1 and +2 for Cu, or +2 and +3 for the other metals .

Types

General

Irwin Fridovich and Joe McCord at Duke University discovered the enzymatic activity of superoxide dismutase in 1968.[4] SODs were previously known as a group of metalloproteins with unknown function; for example, CuZnSOD was known as erythrocuprein (or hemocuprein, or cytocuprein) or as the veterinary anti-inflammatory drug "Orgotein".[5] Likewise, Brewer (1967) identified a protein that later became known as superoxide dismutase as an indophenol oxidase by protein analysis of starch gels using the phenazine-tetrazolium technique.[6]

There are three major families of superoxide dismutase, depending on the protein fold and the metal cofactor: the Cu/Zn type (which binds both copper and zinc), Fe and Mn types (which bind either iron or manganese), and the Ni type (which binds nickel).

Symbol:Sod_Cu
Copper/zinc superoxide dismutase
Pfam:PF00080
Interpro:IPR001424
Prosite:PDOC00082
Scop:1sdy
Symbol:Sod_Fe_N
Iron/manganese superoxide dismutases, alpha-hairpin domain
Pfam:PF00081
Interpro:IPR001189
Prosite:PDOC00083
Scop:1n0j
Symbol:Sod_Fe_C
Iron/manganese superoxide dismutases, C-terminal domain
Pfam:PF02777
Interpro:IPR001189
Prosite:PDOC00083
Scop:1n0j
Symbol:Sod_Ni
Nickel superoxide dismutase
Pfam:PF09055
Interpro:IPR014123
Scop:1q0d

In higher plants, SOD isozymes have been localized in different cell compartments. Mn-SOD is present in mitochondria and peroxisomes. Fe-SOD has been found mainly in chloroplasts but has also been detected in peroxisomes, and CuZn-SOD has been localized in cytosol, chloroplasts, peroxisomes, and apoplast.[12] [13]

Human

There are three forms of superoxide dismutase present in humans, in all other mammals, and most chordates. SOD1 is located in the cytoplasm, SOD2 in the mitochondria, and SOD3 is extracellular. The first is a dimer (consists of two units), whereas the others are tetramers (four subunits). SOD1 and SOD3 contain copper and zinc, whereas SOD2, the mitochondrial enzyme, has manganese in its reactive centre. The genes are located on chromosomes 21, 6, and 4, respectively (21q22.1, 6q25.3 and 4p15.3-p15.1).

SOD1, soluble
Caption:Crystal structure of the human SOD1 enzyme (rainbow-color N-terminus = blue, C-terminus = red) complexed with copper (orange sphere) and zinc (grey sphere)[14]
Hgncid:11179
Symbol:SOD1
Altsymbols:ALS, ALS1
Entrezgene:6647
Omim:147450
Refseq:NM_000454
Uniprot:P00441
Ecnumber:1.15.1.1
Chromosome:21
Arm:q
Band:22.1
SOD2, mitochondrial
Caption:Active site of human mitochondrial Mn superoxide dismutase (SOD2)[15]
Hgncid:11180
Symbol:SOD2
Altsymbols:Mn-SOD; IPO-B; MVCD6
Entrezgene:6648
Omim:147460
Refseq:NM_000636
Uniprot:P04179
Ecnumber:1.15.1.1
Chromosome:6
Arm:q
Band:25
SOD3, extracellular
Caption:Crystallographic structure of the tetrameric human SOD3 enzyme (cartoon diagram) complexed with copper and zinc cations (orange and grey spheres respectively)[16]
Hgncid:11181
Symbol:SOD3
Altsymbols:EC-SOD; MGC20077
Entrezgene:6649
Omim:185490
Refseq:NM_003102
Uniprot:P08294
Ecnumber:1.15.1.1
Chromosome:4
Arm:p
Band:ter
Locussupplementarydata:-q21

Plants

In higher plants, superoxide dismutase enzymes (SODs) act as antioxidants and protect cellular components from being oxidized by reactive oxygen species (ROS).[17] ROS can form as a result of drought, injury, herbicides and pesticides, ozone, plant metabolic activity, nutrient deficiencies, photoinhibition, temperature above and below ground, toxic metals, and UV or gamma rays.[18] [19] To be specific, molecular O2 is reduced to (a ROS called superoxide) when it absorbs an excited electron released from compounds of the electron transport chain. Superoxide is known to denature enzymes, oxidize lipids, and fragment DNA.[18] SODs catalyze the production of O2 and from superoxide, which results in less harmful reactants.

When acclimating to increased levels of oxidative stress, SOD concentrations typically increase with the degree of stress conditions. The compartmentalization of different forms of SOD throughout the plant makes them counteract stress very effectively. There are three well-known and -studied classes of SOD metallic coenzymes that exist in plants. First, Fe SODs consist of two species, one homodimer (containing 1–2 g Fe) and one tetramer (containing 2–4 g Fe). They are thought to be the most ancient SOD metalloenzymes and are found within both prokaryotes and eukaryotes. Fe SODs are most abundantly localized inside plant chloroplasts, where they are indigenous. Second, Mn SODs consist of a homodimer and homotetramer species each containing a single Mn(III) atom per subunit. They are found predominantly in mitochondrion and peroxisomes. Third, Cu-Zn SODs have electrical properties very different from those of the other two classes. These are concentrated in the chloroplast, cytosol, and in some cases the extracellular space. Note that Cu-Zn SODs provide less protection than Fe SODs when localized in the chloroplast.[17] [18] [19]

Bacteria

Human white blood cells use enzymes such as NADPH oxidase to generate superoxide and other reactive oxygen species to kill bacteria. During infection, some bacteria (e.g., Burkholderia pseudomallei) therefore produce superoxide dismutase to protect themselves from being killed.[20]

Biochemistry

SOD out-competes damaging reactions of superoxide, thus protecting the cell from superoxide toxicity.The reaction of superoxide with non-radicals is spin-forbidden. In biological systems, this means that its main reactions are with itself (dismutation) or with another biological radical such as nitric oxide (NO) or with a transition-series metal. The superoxide anion radical spontaneously dismutes to O2 and hydrogen peroxide quite rapidly (~105 M−1s−1 at pH 7). SOD is necessary because superoxide reacts with sensitive and critical cellular targets. For example, it reacts with the NO radical, and makes toxic peroxynitrite.

Because the uncatalysed dismutation reaction for superoxide requires two superoxide molecules to react with each other, the dismutation rate is second-order with respect to initial superoxide concentration. Thus, the half-life of superoxide, although very short at high concentrations (e.g., 0.05 seconds at 0.1mM) is actually quite long at low concentrations (e.g., 14 hours at 0.1 nM). In contrast, the reaction of superoxide with SOD is first order with respect to superoxide concentration. Moreover, superoxide dismutase has the largest kcat/KM (an approximation of catalytic efficiency) of any known enzyme (~7 x 109 M−1s−1),[21] this reaction being limited only by the frequency of collision between itself and superoxide. That is, the reaction rate is "diffusion-limited".

The high efficiency of superoxide dismutase seems necessary: even at the subnanomolar concentrations achieved by the high concentrations of SOD within cells, superoxide inactivates the citric acid cycle enzyme aconitase, can poison energy metabolism, and releases potentially toxic iron. Aconitase is one of several iron-sulfur-containing (de)hydratases in metabolic pathways shown to be inactivated by superoxide.[22]

Stability and folding mechanism

SOD1 is an extremely stable protein. In the holo form (both copper and zinc bound) the melting point is > 90 °C. In the apo form (no copper or zinc bound) the melting point is ~60 °C.[23] By differential scanning calorimetry (DSC), holo SOD1 unfolds by a two-state mechanism: from dimer to two unfolded monomers. In chemical denaturation experiments, holo SOD1 unfolds by a three-state mechanism with observation of a folded monomeric intermediate.[24]

Physiology

Superoxide is one of the main reactive oxygen species in the cell. As a consequence, SOD serves a key antioxidant role. The physiological importance of SODs is illustrated by the severe pathologies evident in mice genetically engineered to lack these enzymes. Mice lacking SOD2 die several days after birth, amid massive oxidative stress.[25] Mice lacking SOD1 develop a wide range of pathologies, including hepatocellular carcinoma,[26] an acceleration of age-related muscle mass loss,[27] an earlier incidence of cataracts, and a reduced lifespan. Mice lacking SOD3 do not show any obvious defects and exhibit a normal lifespan, though they are more sensitive to hyperoxic injury.[28] Knockout mice of any SOD enzyme are more sensitive to the lethal effects of superoxide-generating compounds, such as paraquat and diquat (herbicides).

Drosophila lacking SOD1 have a dramatically shortened lifespan, whereas flies lacking SOD2 die before birth. Depletion of SOD1 and SOD2 in the nervous system and muscles of Drosophila is associated with reduced lifespan.[29] The accumulation of neuronal and muscular ROS appears to contribute to age-associated impairments. When overexpression of mitochondrial SOD2 is induced, the lifespan of adult Drosophila is extended.[30]

Among black garden ants (Lasius niger), the lifespan of queens is an order of magnitude greater than of workers despite no systematic nucleotide sequence difference between them.[31] The SOD3 gene was found to be the most differentially over-expressed in the brains of queen vs worker ants. This finding raises the possibility of an important role of antioxidant function in modulating lifespan.[31]

SOD knockdowns in the worm C. elegans do not cause major physiological disruptions. However, the lifespan of C. elegans can be extended by superoxide/catalase mimetics suggesting that oxidative stress is a major determinant of the rate of aging.[32]

Knockout or null mutations in SOD1 are highly detrimental to aerobic growth in the budding yeast Saccharomyces cerevisiae and result in a dramatic reduction in post-diauxic lifespan. In wild-type S. cerevisiae, DNA damage rates increased 3-fold with age, but more than 5-fold in mutants deleted for either the SOD1 or SOD2 genes.[33] Reactive oxygen species levels increase with age in these mutant strains and show a similar pattern to the pattern of DNA damage increase with age. Thus it appears that superoxide dismutase plays a substantial role in preserving genome integrity during aging in S. cerevisiae.SOD2 knockout or null mutations cause growth inhibition on respiratory carbon sources in addition to decreased post-diauxic lifespan.

In the fission yeast Schizosaccharomyces pombe, deficiency of mitochondrial superoxide dismutase SOD2 accelerates chronological aging.[34]

Several prokaryotic SOD null mutants have been generated, including E. coli. The loss of periplasmic CuZnSOD causes loss of virulence and might be an attractive target for new antibiotics.

Role in disease

Mutations in the first SOD enzyme (SOD1) can cause familial amyotrophic lateral sclerosis (ALS, a form of motor neuron disease).[35] [36] [37] [38] The most common mutation in the U.S. is A4V, while the most intensely studied is G93A. Inactivation of SOD1 causes hepatocellular carcinoma.[26] Diminished SOD3 activity has been linked to lung diseases such as acute respiratory distress syndrome (ARDS) or chronic obstructive pulmonary disease (COPD).[39] [40] [41] Superoxide dismutase is not expressed in neural crest cells in the developing fetus. Hence, high levels of free radicals can cause damage to them and induce dysraphic anomalies (neural tube defects).

Mutations in SOD1 can cause familial ALS (several pieces of evidence also show that wild-type SOD1, under conditions of cellular stress, is implicated in a significant fraction of sporadic ALS cases, which represent 90% of ALS patients.),[42] by a mechanism that is presently not understood, but not due to loss of enzymatic activity or a decrease in the conformational stability of the SOD1 protein. Overexpression of SOD1 has been linked to the neural disorders seen in Down syndrome.[43] In patients with thalassemia, SOD will increase as a form of compensation mechanism. However, in the chronic stage, SOD does not seem to be sufficient and tends to decrease due to the destruction of proteins from the massive reaction of oxidant-antioxidant.[44]

In mice, the extracellular superoxide dismutase (SOD3, ecSOD) contributes to the development of hypertension.[45] [46] Inactivation of SOD2 in mice causes perinatal lethality.[25]

Medical uses

Supplementary superoxide dimutase has been suggested as a treatment to prevent bronchopulmonary dysplasia in infants who are born preterm, however the effectiveness of his treatment is not clear.[47]

Research

SOD has been used in experimental treatment of chronic inflammation in inflammatory bowel conditions.[48] [49] SOD may ameliorate cis-platinum-induced nephrotoxicity (rodent studies).[50] As "Orgotein" or "ontosein", a pharmacologically-active purified bovine liver SOD, it is also effective in the treatment of urinary tract inflammatory disease in man.[51] For a time, bovine liver SOD even had regulatory approval in several European countries for such use. This was cut short by concerns about prion disease.

An SOD-mimetic agent, TEMPOL, is currently in clinical trials for radioprotection and to prevent radiation-induced dermatitis. TEMPOL and similar SOD-mimetic nitroxides exhibit a multiplicity of actions in diseases involving oxidative stress.[52]

The synthesis of enzymes such as superoxide dismutase, L-ascorbate oxidase, and Delta 1 DNA polymerase is initiated in plants with the activation of genes associated with stress conditions for plants.[53] The most common stress conditions can be injury, drought or soil salinity. Limiting this process initiated by the conditions of strong soil salinity can be achieved by administering exogenous glutamine to plants. The decrease in the level of expression of genes responsible for the synthesis of superoxide dismutase increases with the increase in glutamine concentration.[53]

Cosmetic uses

SOD may reduce free radical damage to skin—for example, to reduce fibrosis following radiation for breast cancer. Studies of this kind must be regarded as tentative, however, as there were not adequate controls in the study including a lack of randomization, double-blinding, or placebo.[54] Superoxide dismutase is known to reverse fibrosis, possibly through de-differentiation of myofibroblasts back to fibroblasts.[55]

Commercial sources

SOD is commercially obtained from marine phytoplankton, bovine liver, horseradish, cantaloupe, and certain bacteria. For therapeutic purpose, SOD is usually injected locally. There is no evidence that ingestion of unprotected SOD or SOD-rich foods can have any physiological effects, as all ingested SOD is broken down into amino acids before being absorbed. However, ingestion of SOD bound to wheat proteins could improve its therapeutic activity, at least in theory.[56]

See also

External links

Notes and References

  1. Hayyan M, Hashim MA, AlNashef IM . Superoxide Ion: Generation and Chemical Implications . Chemical Reviews . 116 . 5 . 3029–3085 . March 2016 . 26875845 . 10.1021/acs.chemrev.5b00407 . free .
  2. Archibald FS, Fridovich I. Manganese and Defenses against Oxygen Toxicity in Lactobacillus plantarum. Journal of Bacteriology. 1981. 145. 1. 10.1128/jb.145.1.442-451.1981. 442-451. 6257639. 217292.
  3. Peacock T, Hassan HM. Role of the Mn-Catalase in Aerobic Growth of Lactobacillus plantarum ATCC 14431. Applied Microbiology. 1. 3. 615-625. 10.3390/applmicrobiol1030040. free. 245379268. 2021.
  4. McCord JM, Fridovich I . Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein) . The Journal of Biological Chemistry . 244 . 22 . 6049–6055 . November 1969 . 5389100 . 10.1016/S0021-9258(18)63504-5 . free .
  5. McCord JM, Fridovich I . Superoxide dismutase: the first twenty years (1968–1988) . Free Radical Biology & Medicine . 5 . 5–6 . 363–369 . 1988 . 2855736 . 10.1016/0891-5849(88)90109-8 .
  6. Brewer GJ . Achromatic regions of tetrazolium stained starch gels: inherited electrophoretic variation . American Journal of Human Genetics . 19 . 5 . 674–680 . September 1967 . 4292999 . 1706241 .
  7. Richardson J, Thomas KA, Rubin BH, Richardson DC . Crystal structure of bovine Cu,Zn superoxide dismutase at 3 A resolution: chain tracing and metal ligands . Proceedings of the National Academy of Sciences of the United States of America . 72 . 4 . 1349–1353 . April 1975 . 1055410 . 432531 . 10.1073/pnas.72.4.1349 . free . .
  8. Tainer JA, Getzoff ED, Richardson JS, Richardson DC . Structure and mechanism of copper, zinc superoxide dismutase . Nature . 306 . 5940 . 284–287 . 1983 . 6316150 . 10.1038/306284a0 . 4266810 . 1983Natur.306..284T .
  9. Borgstahl GE, Parge HE, Hickey MJ, Beyer WF, Hallewell RA, Tainer JA . The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles . Cell . 71 . 1 . 107–118 . October 1992 . 1394426 . 10.1016/0092-8674(92)90270-M . 41611695 .
  10. Barondeau DP, Kassmann CJ, Bruns CK, Tainer JA, Getzoff ED . Nickel superoxide dismutase structure and mechanism . Biochemistry . 43 . 25 . 8038–8047 . June 2004 . 15209499 . 10.1021/bi0496081 . 10700340 .
  11. Wuerges J, Lee JW, Yim YI, Yim HS, Kang SO, Djinovic Carugo K . Crystal structure of nickel-containing superoxide dismutase reveals another type of active site . Proceedings of the National Academy of Sciences of the United States of America . 101 . 23 . 8569–8574 . June 2004 . 15173586 . 423235 . 10.1073/pnas.0308514101 . free . 2004PNAS..101.8569W .
  12. Corpas FJ, Barroso JB, del Río LA . Peroxisomes as a source of reactive oxygen species and nitric oxide signal molecules in plant cells . Trends in Plant Science . 6 . 4 . 145–150 . April 2001 . 11286918 . 10.1016/S1360-1385(01)01898-2 .
  13. Corpas FJ, Fernández-Ocaña A, Carreras A, Valderrama R, Luque F, Esteban FJ, Rodríguez-Serrano M, Chaki M, Pedrajas JR, Sandalio LM, del Río LA, Barroso JB . 6 . The expression of different superoxide dismutase forms is cell-type dependent in olive (Olea europaea L.) leaves . Plant & Cell Physiology . 47 . 7 . 984–994 . July 2006 . 16766574 . 10.1093/pcp/pcj071 . free .
  14. Cao X, Antonyuk SV, Seetharaman SV, Whitson LJ, Taylor AB, Holloway SP, Strange RW, Doucette PA, Valentine JS, Tiwari A, Hayward LJ, Padua S, Cohlberg JA, Hasnain SS, Hart PJ . 6 . Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis . The Journal of Biological Chemistry . 283 . 23 . 16169–16177 . June 2008 . 18378676 . 2414278 . 10.1074/jbc.M801522200 . free .
  15. Borgstahl GE, Parge HE, Hickey MJ, Johnson MJ, Boissinot M, Hallewell RA, Lepock JR, Cabelli DE, Tainer JA . 6 . Human mitochondrial manganese superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface . Biochemistry . 35 . 14 . 4287–4297 . April 1996 . 8605177 . 10.1021/bi951892w . 7450190 .
  16. Antonyuk SV, Strange RW, Marklund SL, Hasnain SS . The structure of human extracellular copper-zinc superoxide dismutase at 1.7 A resolution: insights into heparin and collagen binding . Journal of Molecular Biology . 388 . 2 . 310–326 . May 2009 . 19289127 . 10.1016/j.jmb.2009.03.026 .
  17. Alscher RG, Erturk N, Heath LS . Role of superoxide dismutases (SODs) in controlling oxidative stress in plants . Journal of Experimental Botany . 53 . 372 . 1331–1341 . May 2002 . 11997379 . 10.1093/jexbot/53.372.1331 . free .
  18. Smirnoff N . The role of active oxygen in the response of plants to water deficit and desiccation . The New Phytologist . 125 . 1 . 27–58 . September 1993 . 33874604 . 10.1111/j.1469-8137.1993.tb03863.x . free .
  19. Raychaudhuri SS, Deng XW . The Role of Superoxide Dismutase in Combating Oxidative Stress in Higher Plants . The Botanical Review . 66 . 1. 89–98 . 2008 . 10.1007/BF02857783 . 7663001 .
  20. Vanaporn M, Wand M, Michell SL, Sarkar-Tyson M, Ireland P, Goldman S, Kewcharoenwong C, Rinchai D, Lertmemongkolchai G, Titball RW . 6 . Superoxide dismutase C is required for intracellular survival and virulence of Burkholderia pseudomallei . Microbiology . 157 . Pt 8 . 2392–2400 . August 2011 . 21659326 . 10.1099/mic.0.050823-0 . free .
  21. Book: Heinrich PC, Löffler G, Petrifies PE . Biochemie und Pathobiochemie (Springer-Lehrbuch) . German. Springer . Berlin . 2006 . 123 . 978-3-540-32680-9 .
  22. Gardner PR, Raineri I, Epstein LB, White CW . Superoxide radical and iron modulate aconitase activity in mammalian cells . The Journal of Biological Chemistry . 270 . 22 . 13399–13405 . June 1995 . 7768942 . 10.1074/jbc.270.22.13399 . free .
  23. Stathopulos PB, Rumfeldt JA, Karbassi F, Siddall CA, Lepock JR, Meiering EM . Calorimetric analysis of thermodynamic stability and aggregation for apo and holo amyotrophic lateral sclerosis-associated Gly-93 mutants of superoxide dismutase . The Journal of Biological Chemistry . 281 . 10 . 6184–6193 . March 2006 . 16407238 . 10.1074/jbc.M509496200 . free .
  24. Rumfeldt JA, Stathopulos PB, Chakrabarrty A, Lepock JR, Meiering EM . Mechanism and thermodynamics of guanidinium chloride-induced denaturation of ALS-associated mutant Cu,Zn superoxide dismutases . Journal of Molecular Biology . 355 . 1 . 106–123 . January 2006 . 16307756 . 10.1016/j.jmb.2005.10.042 .
  25. Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ . 6 . Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase . Nature Genetics . 11 . 4 . 376–381 . December 1995 . 7493016 . 10.1038/ng1295-376 . 10900822 .
  26. Elchuri S, Oberley TD, Qi W, Eisenstein RS, Jackson Roberts L, Van Remmen H, Epstein CJ, Huang TT . 6 . CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life . Oncogene . 24 . 3 . 367–380 . January 2005 . 15531919 . 10.1038/sj.onc.1208207 . free .
  27. Muller FL, Song W, Liu Y, Chaudhuri A, Pieke-Dahl S, Strong R, Huang TT, Epstein CJ, Roberts LJ, Csete M, Faulkner JA, Van Remmen H . 6 . Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy . Free Radical Biology & Medicine . 40 . 11 . 1993–2004 . June 2006 . 16716900 . 10.1016/j.freeradbiomed.2006.01.036 .
  28. Sentman ML, Granström M, Jakobson H, Reaume A, Basu S, Marklund SL . Phenotypes of mice lacking extracellular superoxide dismutase and copper- and zinc-containing superoxide dismutase . The Journal of Biological Chemistry . 281 . 11 . 6904–6909 . March 2006 . 16377630 . 10.1074/jbc.M510764200 . free .
  29. Oka S, Hirai J, Yasukawa T, Nakahara Y, Inoue YH . A correlation of reactive oxygen species accumulation by depletion of superoxide dismutases with age-dependent impairment in the nervous system and muscles of Drosophila adults . Biogerontology . 16 . 4 . 485–501 . August 2015 . 25801590 . 10.1007/s10522-015-9570-3 . 18050827 .
  30. Sun J, Folk D, Bradley TJ, Tower J . Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster . Genetics . 161 . 2 . 661–672 . June 2002 . 12072463 . 1462135 . 10.1093/genetics/161.2.661 .
  31. Lucas ER, Keller L . Elevated expression of ageing and immunity genes in queens of the black garden ant . Experimental Gerontology . 108 . 92–98 . July 2018 . 29625209 . 10.1016/j.exger.2018.03.020 . 5045743 . free .
  32. Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE, Wallace DC, Malfroy B, Doctrow SR, Lithgow GJ . 6 . Extension of life-span with superoxide dismutase/catalase mimetics . Science . 289 . 5484 . 1567–1569 . September 2000 . 10968795 . 10.1126/science.289.5484.1567 . 21519801 . 2000Sci...289.1567M .
  33. Muid KA, Karakaya HÇ, Koc A . Absence of superoxide dismutase activity causes nuclear DNA fragmentation during the aging process . Biochemical and Biophysical Research Communications . 444 . 2 . 260–263 . February 2014 . 24462872 . 10.1016/j.bbrc.2014.01.056 . free . 11147/5542 .
  34. Ogata T, Senoo T, Kawano S, Ikeda S . Mitochondrial superoxide dismutase deficiency accelerates chronological aging in the fission yeast Schizosaccharomyces pombe . Cell Biology International . 40 . 1 . 100–106 . January 2016 . 26507459 . 10.1002/cbin.10556 . 205563521 . free .
  35. Milani P, Gagliardi S, Cova E, Cereda C . SOD1 Transcriptional and Posttranscriptional Regulation and Its Potential Implications in ALS . Neurology Research International . 2011 . 458427 . 2011 . 21603028 . 3096450 . 10.1155/2011/458427 . free .
  36. Deng HX, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung WY, Getzoff ED, Hu P, Herzfeldt B, Roos RP . 6 . Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase . Science . 261 . 5124 . 1047–1051 . August 1993 . 8351519 . 10.1126/science.8351519 . 1993Sci...261.1047D .
  37. Conwit RA . Preventing familial ALS: a clinical trial may be feasible but is an efficacy trial warranted? . Journal of the Neurological Sciences . 251 . 1–2 . 1–2 . December 2006 . 17070848 . 10.1016/j.jns.2006.07.009 . 33105812 .
  38. Al-Chalabi A, Leigh PN . Recent advances in amyotrophic lateral sclerosis . Current Opinion in Neurology . 13 . 4 . 397–405 . August 2000 . 10970056 . 10.1097/00019052-200008000-00006 . 21577500 .
  39. Young RP, Hopkins R, Black PN, Eddy C, Wu L, Gamble GD, Mills GD, Garrett JE, Eaton TE, Rees MI . 6 . Functional variants of antioxidant genes in smokers with COPD and in those with normal lung function . Thorax . 61 . 5 . 394–399 . May 2006 . 16467073 . 2111196 . 10.1136/thx.2005.048512 .
  40. Ganguly K, Depner M, Fattman C, Bein K, Oury TD, Wesselkamper SC, Borchers MT, Schreiber M, Gao F, von Mutius E, Kabesch M, Leikauf GD, Schulz H . 6 . Superoxide dismutase 3, extracellular (SOD3) variants and lung function . Physiological Genomics . 37 . 3 . 260–267 . May 2009 . 19318538 . 2685504 . 10.1152/physiolgenomics.90363.2008 .
  41. Gongora MC, Lob HE, Landmesser U, Guzik TJ, Martin WD, Ozumi K, Wall SM, Wilson DS, Murthy N, Gravanis M, Fukai T, Harrison DG . 6 . Loss of extracellular superoxide dismutase leads to acute lung damage in the presence of ambient air: a potential mechanism underlying adult respiratory distress syndrome . The American Journal of Pathology . 173 . 4 . 915–926 . October 2008 . 18787098 . 2543061 . 10.2353/ajpath.2008.080119 .
  42. Gagliardi S, Cova E, Davin A, Guareschi S, Abel K, Alvisi E, Laforenza U, Ghidoni R, Cashman JR, Ceroni M, Cereda C . 6 . SOD1 mRNA expression in sporadic amyotrophic lateral sclerosis . Neurobiology of Disease . 39 . 2 . 198–203 . August 2010 . 20399857 . 10.1016/j.nbd.2010.04.008 . 207065284 .
  43. Groner Y, Elroy-Stein O, Avraham KB, Schickler M, Knobler H, Minc-Golomb D, Bar-Peled O, Yarom R, Rotshenker S . 6 . Cell damage by excess CuZnSOD and Down's syndrome . Biomedicine & Pharmacotherapy . 48 . 5–6 . 231–240 . 1994 . 7999984 . 10.1016/0753-3322(94)90138-4 .
  44. Rujito L, Mulatsih S, Sofro AS . Status of Superoxide Dismutase in Transfusion Dependent Thalassaemia . North American Journal of Medical Sciences . 7 . 5 . 194–198 . May 2015 . 26110130 . 4462814 . 10.4103/1947-2714.157480 . free .
  45. Gongora MC, Qin Z, Laude K, Kim HW, McCann L, Folz JR, Dikalov S, Fukai T, Harrison DG . 6 . Role of extracellular superoxide dismutase in hypertension . Hypertension . 48 . 3 . 473–481 . September 2006 . 16864745 . 10.1161/01.HYP.0000235682.47673.ab . free .
  46. Lob HE, Marvar PJ, Guzik TJ, Sharma S, McCann LA, Weyand C, Gordon FJ, Harrison DG . 6 . Induction of hypertension and peripheral inflammation by reduction of extracellular superoxide dismutase in the central nervous system . Hypertension . 55 . 2 . 277–83, 6p following 283 . February 2010 . 20008675 . 2813894 . 10.1161/HYPERTENSIONAHA.109.142646 .
  47. Albertella M, Gentyala RR, Paraskevas T, Ehret D, Bruschettini M, Soll R . Superoxide dismutase for bronchopulmonary dysplasia in preterm infants . The Cochrane Database of Systematic Reviews . 2023 . 10 . CD013232 . October 2023 . 37811631 . 10561150 . 10.1002/14651858.CD013232.pub2 . Cochrane Neonatal Group . October 9, 2024 .
  48. Seguí J, Gironella M, Sans M, Granell S, Gil F, Gimeno M, Coronel P, Piqué JM, Panés J . 6 . Superoxide dismutase ameliorates TNBS-induced colitis by reducing oxidative stress, adhesion molecule expression, and leukocyte recruitment into the inflamed intestine . Journal of Leukocyte Biology . 76 . 3 . 537–544 . September 2004 . 15197232 . 10.1189/jlb.0304196 . 15028921 .
  49. Seguí J, Gironella M, Sans M, Granell S, Gil F, Gimeno M, Coronel P, Piqué JM, Panés J . 6 . Superoxide dismutase ameliorates TNBS-induced colitis by reducing oxidative stress, adhesion molecule expression, and leukocyte recruitment into the inflamed intestine . Journal of Leukocyte Biology . 76 . 3 . 537–544 . September 2004 . 15197232 . 10.1189/jlb.0304196 . 15028921 . free .
  50. McGinness JE, Proctor PH, Demopoulos HB, Hokanson JA, Kirkpatrick DS . Amelioration of cis-platinum nephrotoxicity by orgotein (superoxide dismutase) . Physiological Chemistry and Physics . 10 . 3 . 267–277 . 1978 . 733940 .
  51. Marberger H, Huber W, Bartsch G, Schulte T, Swoboda P . Orgotein: a new antiinflammatory metalloprotein drug evaluation of clinical efficacy and safety in inflammatory conditions of the urinary tract . International Urology and Nephrology . 6 . 2 . 61–74 . 1974 . 4615073 . 10.1007/bf02081999 . 23880216 .
  52. Wilcox CS . Effects of tempol and redox-cycling nitroxides in models of oxidative stress . Pharmacology & Therapeutics . 126 . 2 . 119–145 . May 2010 . 20153367 . 2854323 . 10.1016/j.pharmthera.2010.01.003 .
  53. Kamile . Ulukapi . Ayse Gul . Nasircilar . The role of exogenous glutamine on germination, plant development and transcriptional expression of some stress-related genes in onion under salt stres . . 36 . 1 . 1–17 . February 2024 . 10.2478/fhort-2024-0002 . Polish Society of Horticultural Science . 19887643 . free .
  54. Campana F, Zervoudis S, Perdereau B, Gez E, Fourquet A, Badiu C, Tsakiris G, Koulaloglou S . 6 . Topical superoxide dismutase reduces post-irradiation breast cancer fibrosis . Journal of Cellular and Molecular Medicine . 8 . 1 . 109–116 . 2004 . 15090266 . 6740277 . 10.1111/j.1582-4934.2004.tb00265.x . 10.1.1.336.8033 .
  55. Vozenin-Brotons MC, Sivan V, Gault N, Renard C, Geffrotin C, Delanian S, Lefaix JL, Martin M . 6 . Antifibrotic action of Cu/Zn SOD is mediated by TGF-beta1 repression and phenotypic reversion of myofibroblasts . Free Radical Biology & Medicine . 30 . 1 . 30–42 . January 2001 . 11134893 . 10.1016/S0891-5849(00)00431-7 .
  56. Romao S . Therapeutic value of oral supplementation with melon superoxide dismutase and wheat gliadin combination . Nutrition . 31 . 3 . 430–436 . March 2015 . 25701330 . 10.1016/j.nut.2014.10.006 . free .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Superoxide dismutase".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.