Relationship: 1765



Binding, SH/SeH proteins involved in protection against oxidative stress leads to Protection against oxidative stress, decreased

Upstream event


Binding, SH/SeH proteins involved in protection against oxidative stress

Downstream event


Protection against oxidative stress, decreased

Key Event Relationship Overview


AOPs Referencing Relationship


Taxonomic Applicability


Term Scientific Term Evidence Link
rat Rattus norvegicus NCBI
mouse Mus musculus NCBI
human Homo sapiens NCBI

Sex Applicability


Sex Evidence

Life Stage Applicability


Term Evidence
All life stages High

Key Event Relationship Description


Thiol (SH) and selenol (SeH) compounds exhibit reactivity toward electrophiles and oxidants and have high binding affinities for metals (Higdon, 2012; Nagy, 2013; Winterbourn, 2008; Winther, 2014). Glutathione is a thiol-containing tripeptide acting as a cofactor for the enzyme peroxidase and thus serving as an indirect antioxidant donating the electrons necessary for its decomposition of H2O2, and is also involved in many other cellular functions (Kohen, 2002). Selenoproteins contain selenocysteine amino acid residues. The selenoprotein family is composed of proteins exerting diverse functions, among them several are oxidoreductases classified as antioxidant enzymes (Labunskyy, 2014; Reeves, 2009). Relevant for this KER there are two well-studied selenoprotein families which are described to be expressed in the brain; (i) the Glutathione Peroxidase (GPx) family, involved in detoxification of hydroperoxides; (ii) the Thioredoxin Reductase (TrxR) family, involved in the regeneration of reduced thioredoxin (Pillai, 2014), but also the less studied SelH, K, S, R, W, and P selenoproteins (Pisoschi, 2015; Reeves, 2009).

As summarized in the table 1, binding to the thiol/selenol groups of the selenoproteins cited above can result in structural modifications of these proteins, which in turn inhibits their catalytic activity and thereby reduces or blocks their metabolic capacity to neutralize reactive oxygen species (Fernandes, 1996; Rajanna, 1995). Similarly, binding to the thiol group of glutathione will decrease its anti-oxidant capacity.


Figure (Poole, 2015) Structures of cysteinyl and selenocysteinyl residues within proteins. The aminoacyl groups are shown to the left, with dotted lines representing peptide bonds to the next residue on either side. Both protonated (left) and deprotonated (right) forms of these amino acids are depicted with average pKa values.





Evidence Supporting this KER


Biological Plausibility


GPx family

GPxs are tetrameric enzymes. Their thiol groups can either act directly as a reductant, or catalyze reduction of hydrogen peroxide and/or phospholipid hydroperoxides through glutathione co-factors (Hanschmann, 2013, Labunskyy, 2014).

TrxR family

TxRs are homodimeric flavoenzymes, which mediate the reduction of oxidized Txn at the expense of NADPH (Birben, 2012). Inhibition of TrxR enzymes has been shown to lead to oxidative stress (Branco, 2017).


Downregulation of intracellular SelP by use of small interfering RNA (siRNA) impaired the viability of human astrocytes and made them more susceptible to hydroperoxide-induced oxidative stress, pointing to a direct contribution of SeP to ROS clearance (Steinbrenner, 2006).

Table 1

Selenoprotein family

Protein name

Normal brain function

Disruption leading to oxidative stress




GSH is a major endogenous antioxidant functioning directly in neutralization of free radicals and reactive oxygen compounds. GSH is the reduced form of glutathione and its SH group of cysteine is able to reduce and/or maintain reduced form of other molecules.

Disruptions leads to increased oxidative stress and apoptosis.

Hall, 1999

Dringen, 2000


Glutathione Peroxidase (GPx) Family


Peroxide/ROS reduction

(Promotes neuroprotection in response to oxidative challenge).


Brain expression levels are highest in microglia and lower levels detected in neurons.

Brains of GPx1−/− mice are more vulnerable to mitochondrial toxin treatment, ischemia/ reperfusion, and cold-induced brain injury.

Cultured neurons from GPx1−/− mice were reported to be more susceptible to Aβ-induced oxidative stress, and addition of ebselen reversed this.

Lindenau, 1998

Klivenyi, 2000

Flentjar, 2002

Crack, 2001 and 2006



Reduction of phospholipid


Only in neurons during normal conditions.

Brains of GPx4+/− mice were shown to have increased lipid peroxidation (a sign of oxidative stress).

Injury-induced GPx4 expression in astrocytes.

In vivo over expression of GPx4 protects against oxidative stress-induced apoptosis.

Ran, 2004

Borchert, 2006

Savaskan, 2007

Chen, 2008


Thioredoxin Reductase (TrxR) Family



Cytocsolic, mitochondrial, nuclear localization. Contribute to the reduction of hydrogen peroxide and oxidative stress, and regulates redox-sensitive

transcription factors that

control cellular transcription


Regulate the induction of the antioxidant enzyme heme oxygenase 1 (HO-1).

Overexpression of human Trx1 and Trx2 protects retinal ganglion cells against oxidative stress-induced neurodegeneration.

Exogenously administered human rTrx ameliorates neuronal damage after transient middle cerebral artery occlusion in mice, reduces oxidative/nitrative stress and neuronal apoptosis after cerebral ischemia/reperfusion injury in mice

Gladyshev, 1996

Zhong, 2000

Hattori, 2004

Trigona, 2006

Papp, 2007

Munemasa, 2008

Arbogast, 2010

Ma, 2012

Burk, 2013

Pitts, 2014




Other relevant seleno- proteins


Nuclear localization. Redox sensing.

Hypersensitivity of SelH shRNA HeLa cells to paraquat- and H2O2-induced oxidative stress.


(Panee, 2007)(Novoselov, 2007)

(Wu, 2014)


Transmembrane protein

localized to the ER membrane.

ER homeostasis and oxidative stress response.

Protects HepG2 cells from ER stress agent-induced apoptosis.

Overexpression of SelK attenuated the intracellular reactive oxygen species level and protected cells from oxidative stress-induced toxicity in cardiomyocytes

(Shchedrina, 2011)

(Du, 2010)

(Lu, 2006)


Transmembrane protein

localized to the ER membrane. Catalyze the reduction of disulfide bonds and peroxides.

SelS overexpression increased astrocyte resistance to ER-stress and inflammatory stimuli, and suppression of SelS compromised astrocyte viability.

(Liu, 2013)

(Fradejas, 2011)

(Fradejas, 2008)

 (Gao, 2007)

MSRB1, SelR, SelX

Function in reduction of oxidized methionine residues, and actin polymerization.

Induce expression of MSRB1 protects neurons from amyloid β-protein insults in vitro and in vivo.

(Lee, 2013)

(Moskovitz, 2011)(Pillai, 2014)


Expressed in synapses. Plays an antioxidant role in cells.

Rat in vivo overexpression of SelW was shown to protect glial cells against oxidative stress caused by heavy metals and 2,20-Azobis.

Silencing of SelW made neurons more sensitive to oxidative stress.

(Reeves, 2009)

(Sun, 2001)

(Loflin, 2006)

(Raman, 2013)

(Chung, 2009)


Is important for selenium transport, distribution and retention within the brain.

Acts as a ROS-detoxifying enzyme.

Protects human astrocytes from induced oxidative.

SelP-/- mice show neurological dysfunction and that Se content and GPx activity were reduced within brain, Se supplementation to diet attenuated. neurological dysfunctions.

SelP-/- mice have reported deficits in PV-interneurons due to diminished antioxidant defense capabilities. Decreased neuronal selenoprotein synthesis may be a functional outcome of SelP

Colocalization of Sel P with amyloid plaques


SelP can function as an antioxidant enzyme against reactive lipid intermediates

(Steinbrenner, 2009)(Arbogast, 2010)(Zhang, 2008)

(Hill, 2003;Hill, 2004)

(Cabungcal, 2006)

(Pitts, 2012)

(Byrns, 2014)



(Schomburg, 2003)


(Rock, 2010)



Empirical Evidence



Thiol- and selenol containing proteins have a high affinity for binding metals which contributes to the target site – brain – distribution of such toxicants (Farina, 2011).

The selenol group (-SeH) of selenocysteines is generally more reactive than thiols (-SH) towards mercury (Sugiura 1976, Khan, 2009). Methyl mercury (MeHg) can target both the GPx and TrxR proteins thereby decreasing protection against oxidative stress and therefore causing increased oxidative stress and neurotoxicity (Branco, 2017, Carvalho, 2008, Farina, 2011).

Note: The binding of HgCl2 and MeHg is always studied in vitro on the isolated protein, whereas the effects on the activity of the proteins involved in protection against oxidative stress is mostly studied in isolated cells, mitochondrial fractions or in animals. Therefore the concentrations cannot be compared. Binding of Hg to thiol groups and to various selenium-containing proteins: Glutathione, thioredoxin reductase, thioredoxin, glutaredoxin, glutathione reductase was measured using purified proteins (Carvahlo et al., 2008, 2011; Wiederhold et al., 2010; Sugiura et al., 1978; Arnold et al., 1986; Han et al., 2001; Qiao et al., 2017).



Table 2


Binding, Thiol/seleno-proteins involved in protection against oxidative stress


Decreased protection against oxidative stress


Species; in vivo / in vitro






Dose/ conc. +

Duration of exp.

Protective/ aggravating evidence





Binding of 2.5 mol of Hg2+ /mol of TrX1

(Carvahlo et al., 2008)

Inhibition of TrX

Inhibition of TrXR

Recombinant rat TrX

HeLa and HEK293 cells


IC50 7.2 nM

Selenite (5 mM)

(Carvahlo et al., 2008, 2011)

Binding of 5 mol of Hg2+ /mol of TrX1

(Carvahlo et al., 2008)

Inhibition of TrX

Inhibition of TrXR

Recombinant rat TrX

HeLa and HEK293 cells


IC50 19.7 nM

Selenite (5 mM)

(Carvahlo et al., 2008, 2011)

Binding to GR and GrX (Carvahlo et al., 2008)

Total inhibition

Purified proteins


10 nM


(Carvahlo et al., 2008)

Binding to GR and GrX (Carvahlo et al., 2008)

50% of inhibition

Purified proteins


80 nM


(Carvahlo et al. 2008)


Inhibition of TrxR and GSH activities.

TrxR activity – cytosolic: 0.7 fold; mitochondrial: 0.4 fold)



TrxR1&2 expression – slight decrease, not quantified

GSH – 0.7-fold

Human neuroblastoma cells (SH-SY5Y)


1 µM



(Branco, 2017)


Depletion of GSH levels.


10µM – 0.75-fold

30µM – 0.6-fold

100µM – 0,5-fold

Mouse brain mito-chondrial-enriched



10, 30, and 100 μM


30 minutes

The co-incubation with diphenyl diselenide (100 μM)completely prevented the disruption of mitochondrial activity.

(Meinerz, 2011)


Depleted GSH levels.

Adult male Wistar rats


30ppm in drinking water


(Agrawal, 2015)


Acrylamide (acrylamide is a common food contaminant generated by heat processing)

No literature supporting the link “SH/SeH binding leads to decreased protection against oxidative stress” for acrylamide as stressor in brain/neural tissue can be found.

Uncertainties and Inconsistencies


Another important group of thiol-containing proteins are the metal-binging detoxifying metallothioneins. This protein family bind mercury and lead, and this binding thus serves as a protective mechanism and also protects against metal toxicity and oxidative stress (Aschner, 2006).

Lactational exposure to methylmercury (10 mg/L in drinking water) significantly increased cerebellar GSH level and GR activity. Possibly a compensatory response to mercury-induced oxidative stress (Franco, 2006).

MeHg was shown to inhibit cerebral thioredoxin reductase activity in vitro but not in brain of mice (Wagner et al., 2010). However, it has to be noted that the exposure of mice to MeHg was only 24h.

Inhibition og GR and GrX by Hg2+ and MeHg was observed on the puried protein, but not in HeLa cells incubated with the same concentrations for 24h (Carvahlo et al., 2008).

Quantitative Understanding of the Linkage


See Table 2

Response-response Relationship




Known modulating factors


Known Feedforward/Feedback loops influencing this KER


Domain of Applicability


Experimental evidences has been observed in rat, mice and human cells (Agrawal, 2015; Meinerz, 2011; Branco, 2017)



Agrawal, S. et al. (2015) Changes in tissue oxidative stress, brain biogenic amines and acetylcholinesterase following co-exposure to lead, arsenic and mercury in rats. Food Chem Toxicol 86, 208-216.

Arbogast, S., Ferreiro, A. (2010) Selenoproteins and protection against oxidative stress: selenoprotein N as a novel player at the crossroads of redox signaling and calcium homeostasis. Antioxid Redox Signal 12, 893-904.

Arnold AP, Khoon ST, Rabenstein DL (1986) Nuclear magnetic resonance studies of the solution chemistry of metal complexes. 23. Complexation of methylmercury by selenohydryl-containing amino acids and related molecules. Inorganic Chemistry 25 (14), 2433-2437.

Aschner, M. et al. (2006) Metallothioneins: mercury species-specific induction and their potential role in attenuating neurotoxicity. Exp Biol Med (Maywood) 231, 1468-1473.

Birben, E. et al. (2012) Oxidative stress and antioxidant defense. World Allergy Organ J 5, 9-19.

Borchert, A. et al. (2006) The role of phospholipid hydroperoxide glutathione peroxidase isoforms in murine embryogenesis. J Biol Chem 281, 19655-19664.

Branco, V. et al. (2017) Impaired cross-talk between the thioredoxin and glutathione systems is related to ASK-1 mediated apoptosis in neuronal cells exposed to mercury. Redox Biol 13, 278-287.

Burk, R.F. et al. (2013) Maternal-fetal transfer of selenium in the mouse. FASEB J 27, 3249-3256.

Byrns, C.N. et al. (2014) Mice lacking selenoprotein P and selenocysteine lyase exhibit severe neurological dysfunction, neurodegeneration, and audiogenic seizures. J Biol Chem 289, 9662-9674.

Cabungcal, J.H. et al. (2006) Glutathione deficit during development induces anomalies in the rat anterior cingulate GABAergic neurons: Relevance to schizophrenia. Neurobiol Dis 22, 624-637.

Carvalho, C.M. et al. (2008) Inhibition of the human thioredoxin system. A molecular mechanism of mercury toxicity. J Biol Chem 283, 11913-11923.

Carvalho, C.M.L. et al. (2011), Effects of selenite and chelating agents on mammalian thioredoxin reductase inhibited by mercury: Implications for treatment of mercury poisoning(. FASEB Journal, 25 (1), pp. 370-381.

Chen, L. et al. (2008) Lipid peroxidation up-regulates BACE1 expression in vivo: a possible early event of amyloidogenesis in Alzheimer's disease. J Neurochem 107, 197-207.

Chung, Y.W. et al. (2009) Antioxidative role of selenoprotein W in oxidant-induced mouse embryonic neuronal cell death. Mol Cells 27, 609-613.

Crack, P.J. et al. (2006) Lack of glutathione peroxidase-1 exacerbates Abeta-mediated neurotoxicity in cortical neurons. J Neural Transm (Vienna) 113, 645-657.

Crack, P.J. et al. (2001) Increased infarct size and exacerbated apoptosis in the glutathione peroxidase-1 (Gpx-1) knockout mouse brain in response to ischemia/reperfusion injury. J Neurochem 78, 1389-1399.

Dringen, R. (2000) Metabolism and functions of glutathione in brain. Prog Neurobiol 62, 649-671.

Du, S. et al. (2010) SelK is a novel ER stress-regulated protein and protects HepG2 cells from ER stress agent-induced apoptosis. Arch Biochem Biophys 502, 137-143.

Farina, M. et al. (2011) Oxidative stress in MeHg-induced neurotoxicity. Toxicol Appl Pharmacol 256, 405-417.

Fernandes, A.C. et al. (1996) Different effects of thiol and nonthiol ace inhibitors on copper-induced lipid and protein oxidative modification. Free Radic Biol Med 20, 507-514.

Flentjar, N.J. et al. (2002) Mice lacking glutathione peroxidase-1 activity show increased TUNEL staining and an accelerated inflammatory response in brain following a cold-induced injury. Exp Neurol 177, 9-20.

Fradejas, N. et al. (2008) SEPS1 gene is activated during astrocyte ischemia and shows prominent antiapoptotic effects. J Mol Neurosci 35, 259-265.

Fradejas, N. et al. (2011) Selenoprotein S expression in reactive astrocytes following brain injury. Glia 59, 959-972.

Franco, J.L. et al. (2006) Cerebellar thiol status and motor deficit after lactational exposure to methylmercury. Environ Res 102, 22-28.

Gao, Y. et al. (2007) Secretion of the glucose-regulated selenoprotein SEPS1 from hepatoma cells. Biochem Biophys Res Commun 356, 636-641.

Gladyshev, V.N. et al. (1996) Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene. Proc Natl Acad Sci U S A 93, 6146-6151.

Hall, A.G. (1999) Review: The role of glutathione in the regulation of apoptosis. Eur J Clin Invest 29, 238-245.

Han S, Zhu M, Yuan Z, Li X (2001) A methylene blue-mediated enzyme electrode for the determination of trace mercury (II), mercury (I), methylmercury, and mercury-glutathione complex. Biosensors & Bioelectronics. 16 : 9-16.

Hanschmann, E.M. et al. (2013) Thioredoxins, glutaredoxins, and peroxiredoxins--molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling. Antioxid Redox Signal 19, 1539-1605.

Hattori, I. et al. (2004) Intravenous administration of thioredoxin decreases brain damage following transient focal cerebral ischemia in mice. Antioxid Redox Signal 6, 81-87.

Higdon, A. et al. (2012) Cell signalling by reactive lipid species: new concepts and molecular mechanisms. Biochem J 442, 453-464.

Hill, K.E. et al. (2003) Deletion of selenoprotein P alters distribution of selenium in the mouse. J Biol Chem 278, 13640-13646.

Hill, K.E. et al. (2004) Neurological dysfunction occurs in mice with targeted deletion of the selenoprotein P gene. J Nutr 134, 157-161.

Khan, M.A.K., Wang, F., 2009. Mercury-selenium compounds an their toxicological significance: topward a molecular understanding of the mercury-selenium antagonism. Environ. Toxicol. Chem. 28 (8), 1567-1577.

Klivenyi, P. et al. (2000) Mice deficient in cellular glutathione peroxidase show increased vulnerability to malonate, 3-nitropropionic acid, and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. J Neurosci 20, 1-7.

Kohen, R., Nyska, A. (2002) Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol 30, 620-650.

Labunskyy, V.M. et al. (2014) Selenoproteins: molecular pathways and physiological roles. Physiol Rev 94, 739-777.

Lee, B.C. et al. (2013) MsrB1 and MICALs regulate actin assembly and macrophage function via reversible stereoselective methionine oxidation. Mol Cell 51, 397-404.

Lindenau, J. et al. (1998) Enhanced cellular glutathione peroxidase immunoreactivity in activated astrocytes and in microglia during excitotoxin induced neurodegeneration. Glia 24, 252-256.

Liu, J., Rozovsky, S. (2013) Contribution of selenocysteine to the peroxidase activity of selenoprotein S. Biochemistry 52, 5514-5516.

Loflin, J. et al. (2006) Selenoprotein W during development and oxidative stress. J Inorg Biochem 100, 1679-1684.

Lu, C. et al. (2006) Identification and characterization of selenoprotein K: an antioxidant in cardiomyocytes. FEBS Lett 580, 5189-5197.

Ma, Y.H. et al. (2012) Thioredoxin-1 attenuates post-ischemic neuronal apoptosis via reducing oxidative/nitrative stress. Neurochem Int 60, 475-483.

Meinerz, D.F. et al. (2011) Protective effects of organoselenium compounds against methylmercury-induced oxidative stress in mouse brain mitochondrial-enriched fractions. Braz J Med Biol Res 44, 1156-1163.

Moskovitz, J. et al. (2011) Induction of methionine-sulfoxide reductases protects neurons from amyloid beta-protein insults in vitro and in vivo. Biochemistry 50, 10687-10697.

Munemasa, Y. et al. (2008) Protective effect of thioredoxins 1 and 2 in retinal ganglion cells after optic nerve transection and oxidative stress. Invest Ophthalmol Vis Sci 49, 3535-3543.

Nagy, P. (2013) Kinetics and mechanisms of thiol-disulfide exchange covering direct substitution and thiol oxidation-mediated pathways. Antioxid Redox Signal 18, 1623-1641.

Novoselov, S.V. et al. (2007) Selenoprotein H is a nucleolar thioredoxin-like protein with a unique expression pattern. J Biol Chem 282, 11960-11968.

Panee, J. et al. (2007) Selenoprotein H is a redox-sensing high mobility group family DNA-binding protein that up-regulates genes involved in glutathione synthesis and phase II detoxification. J Biol Chem 282, 23759-23765.

Papp, L.V. et al. (2007) From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid Redox Signal 9, 775-806.

Pillai, R. et al. (2014) Selenium and selenoprotein function in brain disorders. IUBMB Life 66, 229-239.

Pisoschi, A.M., Pop, A. (2015) The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 97, 55-74.

Pitts, M.W. et al. (2014) Selenoproteins in nervous system development and function. Biol Trace Elem Res 161, 231-245.

Pitts, M.W. et al. (2012) Deletion of selenoprotein P results in impaired function of parvalbumin interneurons and alterations in fear learning and sensorimotor gating. Neuroscience 208, 58-68.

Poole, L.B. (2015) The basics of thiols and cysteines in redox biology and chemistry. Free Radic Biol Med 80, 148-157.

Qiao Y, Huang X, Chen B, He M, Hu B 2017. In vitro study on antagonism mechanism of glutathione, sodium selenite and mercuric chloride. Talanta 171 : 262-269.

Rajanna, B. et al. (1995) Modulation of protein kinase C by heavy metals. Toxicol Lett 81, 197-203.

Raman, A.V. et al. (2013) Selenoprotein W expression and regulation in mouse brain and neurons. Brain Behav 3, 562-574.

Ran, Q. et al. (2004) Transgenic mice overexpressing glutathione peroxidase 4 are protected against oxidative stress-induced apoptosis. J Biol Chem 279, 55137-55146.

Reeves, M.A., Hoffmann, P.R. (2009) The human selenoproteome: recent insights into functions and regulation. Cell Mol Life Sci 66, 2457-2478.

Rock, C., Moos, P.J. (2010) Selenoprotein P protects cells from lipid hydroperoxides generated by 15-LOX-1. Prostaglandins Leukot Essent Fatty Acids 83, 203-210.

Savaskan, N.E. et al. (2007) Role for glutathione peroxidase-4 in brain development and neuronal apoptosis: specific induction of enzyme expression in reactive astrocytes following brain injury. Free Radic Biol Med 43, 191-201.

Schomburg, L. et al. (2003) Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues. Biochem J 370, 397-402.

Shchedrina, V.A. et al. (2011) Selenoprotein K binds multiprotein complexes and is involved in the regulation of endoplasmic reticulum homeostasis. J Biol Chem 286, 42937-42948.

Sugiura Y, Tamai Y, Tanaka H. (1978) Selenium protection against mercury toxicity : high binding affinity of methylmercury by selenium-containing ligands in comparison with sulfur-containing ligands. Bioinorg. Chem. 9 :167-180.

Steinbrenner, H. et al. (2006) Involvement of selenoprotein P in protection of human astrocytes from oxidative damage. Free Radic Biol Med 40, 1513-1523.

Steinbrenner, H., Sies, H. (2009) Protection against reactive oxygen species by selenoproteins. Biochim Biophys Acta 1790, 1478-1485.

Sugiura, Y., et al.(1976), Selenium protection against mercury toxicity. Binding of methylmercury by the selenohydryl-containing ligand. Journal of the American Chemical Society,  98:2339–2341.

Sun, Y. et al. (2001) Selenoprotein W in overexpressed and underexpressed rat glial cells in culture. J Inorg Biochem 84, 151-156.

Trigona, W.L. et al. (2006) Thioredoxin reductase regulates the induction of haem oxygenase-1 expression in aortic endothelial cells. Biochem J 394, 207-216.

Wagner, C., Sudati, J.H., Nogueira, C.W., Rocha, J.B.T. (2010) In vivo and in vitro inhibition of mice thioredoxin reductase by methymercury. Biometals 23, 1171-1177.

Wiederhold JG, Cramer CJ, Daniel K, Infante I, Bourdon B, Kretzschmar R. (2010) Equilibrium mercury isotope fractionation between dissolved Hg(II) species and thiol-bound Hg. Environ Sci Technol. 44 :4191-7. Doi : 10.1021/es100205t.

Winterbourn, C.C., Hampton, M.B. (2008) Thiol chemistry and specificity in redox signaling. Free Radic Biol Med 45, 549-561.

Winther, J.R., Thorpe, C. (2014) Quantification of thiols and disulfides. Biochim Biophys Acta 1840, 838-846.

Wu, R.T. et al. (2014) Selenoprotein H suppresses cellular senescence through genome maintenance and redox regulation. J Biol Chem 289, 34378-34388.

Zhang, Y. et al. (2008) Comparative analysis of selenocysteine machinery and selenoproteome gene expression in mouse brain identifies neurons as key functional sites of selenium in mammals. J Biol Chem 283, 2427-2438.

Zhong, L. et al. (2000) Structure and mechanism of mammalian thioredoxin reductase: the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence. Proc Natl Acad Sci U S A 97, 5854-5859.