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Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized In Cells Treated With Isothiocyanates.

K. Brown, S. Eriksson, Elias S. J. Arnér, M. Hampton
Published 2008 · Chemistry, Medicine

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Isothiocyanates are phytochemicals with anti-cancer properties that include the ability to trigger apoptosis. A substantial body of evidence suggests that reaction of the electrophilic isothiocyanate moiety with cysteine residues in cellular proteins and glutathione accounts for their biological activity. In this study we investigated the effect of several different isothiocyanates on the redox states of the cysteine-dependent peroxiredoxins (Prx) in Jurkat T lymphoma cells, and compared this to known effects on the selenoprotein thioredoxin reductase, glutathione reductase and intracellular GSH levels. Interestingly, oxidation of mitochondrial Prx3 could be detected as early as 5 min after exposure of cells to phenethyl isothiocyanate, with complete oxidation occurring at doses that only had small inhibitory effects on total cellular thioredoxin reductase and glutathione reductase activities. Peroxiredoxin oxidation was specific to the mitochondrial isoform with cytoplasmic Prx1 and Prx2 maintained in their reduced forms at all analyzed time points and concentrations of isothiocyanate. Phenethyl isothiocyanate could react with purified Prx3 directly, but it did not oxidize Prx3 or promote its oxidation by hydrogen peroxide. A selection of aromatic and alkyl isothiocyanates were tested and while all lowered cellular GSH levels, only the isothiocyanates that caused Prx3 oxidation were able to trigger cell death. We propose that pro-apoptotic isothiocyanates selectively disrupt mitochondrial redox homeostasis, as indicated by Prx3 oxidation, and that this contributes to their pro-apoptotic activity.
This paper references
10.1111/j.1558-5646.1978.tb01118.x
Protein Structure and Evolution
W. Fitch (1976)
Use of Isothiocyanates as 'reporter' groups in modification of enzymes
L. Drobnica (1976)
The Chemistry of cyanates and their thio derivatives
S. Patai (1977)
10.1021/AR00009A003
Glutathione: a vehicle for the transport of chemically reactive metabolites in vivo
T. Baillie (1991)
10.1042/BJ3110453
Isothiocyanates as substrates for human glutathione transferases: structure-activity studies.
R. Kolm (1995)
10.1006/BBRC.1995.1106
Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases.
Y. Zhang (1995)
Chemopreventive isothiocyanates induce apoptosis and caspase-3-like protease activity.
R. Yu (1998)
10.1073/PNAS.95.12.6803
Measurement of cytosolic, mitochondrial, and Golgi pH in single living cells with green fluorescent proteins.
J. Llopis (1998)
10.1074/jbc.273.15.8581
Rat and Calf Thioredoxin Reductase Are Homologous to Glutathione Reductase with a Carboxyl-terminal Elongation Containing a Conserved Catalytically Active Penultimate Selenocysteine Residue*
L. Zhong (1998)
10.1074/jbc.273.11.6297
Mammalian Peroxiredoxin Isoforms Can Reduce Hydrogen Peroxide Generated in Response to Growth Factors and Tumor Necrosis Factor-α*
S. W. Kang (1998)
10.1016/S0168-8227(99)00037-6
Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin.
H. Chae (1999)
10.1093/CARCIN/21.11.1983
7-Methylsulfinylheptyl and 8-methylsulfinyloctyl isothiocyanates from watercress are potent inducers of phase II enzymes.
P. Rose (2000)
Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate.
M. Nakajima (2001)
10.1016/S0006-2952(00)00526-8
Involvement of glutathione metabolism in the cytotoxicity of the phenethyl isothiocyanate and its cysteine conjugate to human leukaemia cells in vitro.
K. Xu (2001)
Inhibition of benzo(a)pyrene-induced lung tumorigenesis in A/J mice by dietary N-acetylcysteine conjugates of benzyl and phenethyl isothiocyanates during the postinitiation phase is associated with activation of mitogen-activated protein kinases and p53 activity and induction of apoptosis.
Y. Yang (2002)
10.1042/BJ3640301
High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate.
Y. Zhang (2002)
10.1016/S0076-6879(02)47012-7
High-throughput 96-well microplate assays for determining specific activities of glutathione peroxidase and thioredoxin reductase.
A. Smith (2002)
10.1016/S0968-0004(02)00003-8
Structure, mechanism and regulation of peroxiredoxins.
Z. Wood (2003)
10.1093/CARCIN/BGH136
Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest.
J. Chiao (2004)
10.1093/CARCIN/BGH063
The chemopreventive agent phenethyl isothiocyanate sensitizes cells to Fas-mediated apoptosis.
J. Pullar (2003)
10.1074/JBC.M407707200
Peroxiredoxin III, a Mitochondrion-specific Peroxidase, Regulates Apoptotic Signaling by Mitochondria*
T. Chang (2004)
10.1021/JF030549S
Induction of phase II detoxification enzymes in rats by plant-derived isothiocyanates: comparison of allyl isothiocyanate with sulforaphane and related compounds.
R. Munday (2004)
10.1128/AEM.70.9.5159-5167.2004
Assessment of Production Conditions for Efficient Use of Escherichia coli in High-Yield Heterologous Recombinant Selenoprotein Synthesis
Olle Rengby (2004)
10.1089/ARS.2005.7.1601
Time-dependent modulation of thioredoxin reductase activity might contribute to sulforaphane-mediated inhibition of NF-kappaB binding to DNA.
E. Heiss (2005)
10.1016/J.BBAGEN.2005.05.010
Selenocysteine in proteins-properties and biotechnological use.
L. Johansson (2005)
10.1021/TX0502138
Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane.
F. Hong (2005)
10.1038/sj.onc.1208656
Suppression of NF-κB and NF-κB-regulated gene expression by sulforaphane and PEITC through IκBα, IKK pathway in human prostate cancer PC-3 cells
C. Xu (2005)
10.1038/NCHEMBIO727
Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors
V. Kagan (2005)
10.1007/BF01920581
Reactions of cysteine, its derivatives, glutathione, coenzyme A, and dihydrolipoic acid with isothiocyanates
D. Podhradský (1979)
10.1158/0008-5472.CAN-05-3809
Phenethyl isothiocyanate triggers apoptosis in Jurkat cells made resistant by the overexpression of Bcl-2.
S. Thomson (2006)
10.1016/J.CCR.2006.08.009
Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate.
D. Trachootham (2006)
10.1158/1535-7163.MCT-05-0324
Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention
Elisabeth Bertl (2006)
10.1093/CARCIN/BGI301
Effects of benzyl and phenethyl isothiocyanate on P450s 2A6 and 2A13: potential for chemoprevention in smokers.
L. V. von Weymarn (2006)
10.1083/JCB.200607061
Defective mitochondrial peroxiredoxin-3 results in sensitivity to oxidative stress in Fanconi anemia
S. Mukhopadhyay (2006)
10.1016/J.SEMCANCER.2006.09.004
On the potential of thioredoxin reductase inhibitors for cancer therapy.
Sabine Urig (2006)
10.1096/fj.05-4785fje
Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apcmin mice
M. Myzak (2006)
10.1016/J.ABB.2007.05.001
Mitochondrial thioredoxin-2/peroxiredoxin-3 system functions in parallel with mitochondrial GSH system in protection against oxidative stress.
H. Zhang (2007)
10.1515/BC.2007.135
Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents
Y. Hu (2007)
10.1158/0008-5472.CAN-06-3645
Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo.
D. Xiao (2007)
10.1002/jcb.21241
Peroxiredoxin I and II inhibit H2O2‐induced cell death in MCF‐7 cell lines
Jiyeon Bae (2007)
10.1016/J.BBRC.2007.02.022
Increased susceptibility of MER5 (peroxiredoxin III) knockout mice to LPS-induced oxidative stress.
Lianqin Li (2007)
10.1074/jbc.M700339200
The High Reactivity of Peroxiredoxin 2 with H2O2 Is Not Reflected in Its Reaction with Other Oxidants and Thiol Reagents*
A. Peskin (2007)
10.1016/j.freeradbiomed.2007.11.017
Oxidation of mitochondrial peroxiredoxin 3 during the initiation of receptor-mediated apoptosis.
Andrew G. Cox (2008)
10.1016/j.bbagen.2008.01.011
Redox compartmentalization in eukaryotic cells.
Y. Go (2008)
10.1002/9780470771532.CH6
The chemistry of the — NCS group
L. Drobnica (2010)



This paper is referenced by
10.1016/J.ARRES.2021.100008
Maneb adducts human peroxiredoxin 3 through thiol interactions
C. Anderson (2021)
10.1039/d1fo00423a
Exposure to oxidized soybean oil induces mammary mitochondrial injury in lactating rats and alters the intestinal barrier function of progeny.
Chuanqi Wang (2021)
Studies of the thioredoxin system in redox signaling and oxidative stress
B. Fernández (2020)
10.1007/164_2020_393
Effects of Mammalian Thioredoxin Reductase Inhibitors.
Elias S. J. Arnér (2020)
10.1007/978-3-030-39855-2_9
The Chemopreventive Power of Isothiocyanates
Sharadha Dayalan Naidu (2020)
10.1002/jcp.27322
Heat‐shock protein B1 upholds the cytoplasm reduced state to inhibit activation of the Hippo pathway in H9c2 cells
Xiehong Liu (2018)
10.1016/j.redox.2019.101343
SIRT3-mediated deacetylation of PRDX3 alleviates mitochondrial oxidative damage and apoptosis induced by intestinal ischemia/reperfusion injury
Zhanyu Wang (2019)
10.1002/jcp.27397
Integrative proteomics and immunochemistry analysis of the factors in the necrosis and repair in acetaminophen‐induced acute liver injury in mice
Q. Feng (2018)
10.1016/j.freeradbiomed.2018.10.407
Peroxiredoxin interaction with the cytoskeletal‐regulatory protein CRMP2: Investigation of a putative redox relay
P. Pace (2018)
10.1016/j.freeradbiomed.2017.12.029
The A to Z of modulated cell patterning by mammalian thioredoxin reductases
M. Dagnell (2018)
10.1089/ars.2017.7422
Peroxiredoxin Involvement in the Initiation and Progression of Human Cancer.
M. Hampton (2017)
10.1016/j.freeradbiomed.2017.07.033
Antioxidant defense in quiescent cells determines selectivity of electron transport chain inhibition-induced cell death.
Jan Blecha (2017)
10.1016/j.redox.2017.05.024
Impaired cross-talk between the thioredoxin and glutathione systems is related to ASK-1 mediated apoptosis in neuronal cells exposed to mercury
V. Branco (2017)
10.1016/j.celrep.2017.01.070
Control of Mitochondrial Remodeling by the ATPase Inhibitory Factor 1 Unveils a Pro-survival Relay via OPA1.
D. Faccenda (2017)
10.18632/oncotarget.13723
Inhibition of cancer antioxidant defense by natural compounds
A. Sznarkowska (2016)
10.1201/9781315154831-21
H2O2, Thioredoxin, and Signaling
Elias S. J. Arnér (2017)
Control of Mitochondrial R emodeling by the ATPase Inhibitory Factor 1 Unveils a Pro-survival Relay via OPA 1 Graphical
D. Faccenda (2017)
10.18632/oncotarget.13838
Differential expression of peroxiredoxin 3 in laryngeal squamous cell carcinoma
Hua Zhang (2016)
10.14348/molcells.2016.2351
Peroxiredoxins and the Regulation of Cell Death
M. Hampton (2016)
10.1007/978-3-319-41283-2_16
Thioredoxin Reductase 1 as an Anticancer Drug Target
E. E. Schmidt (2016)
10.1016/j.freeradbiomed.2015.12.008
Enhanced targeting of mitochondrial peroxide defense by the combined use of thiosemicarbazones and inhibitors of thioredoxin reductase.
C. Myers (2016)
10.1074/jbc.M116.726968
Compartment-specific Control of Reactive Oxygen Species Scavenging by Antioxidant Pathway Enzymes*
Swati Dey (2016)
10.1007/s11596-015-1393-6
Formaldehyde induces the bone marrow toxicity in mice by regulating the expression of Prx3 protein
G. Yu (2015)
10.1089/ars.2015.6378
TrxR1 as a potent regulator of the Nrf2-Keap1 response system.
M. Cebula (2015)
10.1007/s11596-015-1393-6
Formaldehyde induces the bone marrow toxicity in mice by regulating the expression of Prx3 protein
Guang-yan Yu 于光艳 (2015)
10.1016/bs.enz.2015.05.003
Anticancer Mechanism of Sulfur-Containing Compounds.
Elena de Gianni (2015)
10.1007/s00432-015-1916-3
The functional role of peroxiredoxin 3 in reactive oxygen species, apoptosis, and chemoresistance of cancer cells
Lianqin Li (2015)
10.1016/j.bbagen.2013.08.001
Peroxiredoxins as biomarkers of oxidative stress.
Rebecca A. Poynton (2014)
10.1186/2049-3002-2-4
A strategically designed small molecule attacks alpha-ketoglutarate dehydrogenase in tumor cells through a redox process
S. Stuart (2014)
10.1002/elps.201300378
Comparative proteomics analysis of host cells infected with Brucella abortus A19
Yongping Wu (2014)
Intricate aspects of the thioredoxin system in redox signaling
M. Cebula (2014)
10.1016/j.fob.2012.12.002
Anti-apoptotic role of peroxiredoxin III in cervical cancer cells☆
Lianqin Li (2012)
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