TrxR1, Gsr, and oxidative stress determine hepatocellular carcinoma malignancy.
Animals
Antioxidants
/ metabolism
Carcinoma, Hepatocellular
/ metabolism
DNA Damage
/ physiology
Disease Progression
Gene Expression Regulation
/ physiology
Glutathione
/ metabolism
Glutathione Reductase
/ metabolism
Hepatocytes
/ metabolism
Liver
/ metabolism
Liver Neoplasms
/ metabolism
Male
Metabolome
/ physiology
Mice
NF-E2-Related Factor 2
/ metabolism
Oxidation-Reduction
Oxidative Stress
/ physiology
Thioredoxin Reductase 1
/ metabolism
Nrf2
glutathione reductase
hepatocellular carcinoma
oxidative stress
thioredoxin reductase
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
04 06 2019
04 06 2019
Historique:
pubmed:
18
5
2019
medline:
24
3
2020
entrez:
18
5
2019
Statut:
ppublish
Résumé
Thioredoxin reductase-1 (TrxR1)-, glutathione reductase (Gsr)-, and Nrf2 transcription factor-driven antioxidant systems form an integrated network that combats potentially carcinogenic oxidative damage yet also protects cancer cells from oxidative death. Here we show that although unchallenged wild-type (WT), TrxR1-null, or Gsr-null mouse livers exhibited similarly low DNA damage indices, these were 100-fold higher in unchallenged TrxR1/Gsr-double-null livers. Notwithstanding, spontaneous cancer rates remained surprisingly low in TrxR1/Gsr-null livers. All genotypes, including TrxR1/Gsr-null, were susceptible to
Identifiants
pubmed: 31097586
pii: 1903244116
doi: 10.1073/pnas.1903244116
pmc: PMC6561278
doi:
Substances chimiques
Antioxidants
0
NF-E2-Related Factor 2
0
Glutathione Reductase
EC 1.8.1.7
Thioredoxin Reductase 1
EC 1.8.1.9
Txnrd1 protein, mouse
EC 1.8.1.9
Glutathione
GAN16C9B8O
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11408-11417Subventions
Organisme : NIGMS NIH HHS
ID : P30 GM110732
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG040020
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA152559
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123738
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG055022
Pays : United States
Organisme : NIH HHS
ID : R21 OD026444
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA215784
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103474
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Toxicol Pathol. 2000 Mar-Apr;28(2):215-25
pubmed: 10805139
Free Radic Biol Med. 2000 May 1;28(9):1387-404
pubmed: 10924858
Biochemistry. 2000 Oct 24;39(42):13005-11
pubmed: 11041866
Br J Cancer. 1953 Mar;7(1):68-72
pubmed: 13051507
Annu Rev Nutr. 2004;24:539-77
pubmed: 15189131
Toxicol Sci. 2004 Dec;82(2):367-73
pubmed: 15342956
Trends Mol Med. 2004 Nov;10(11):549-57
pubmed: 15519281
Cell. 2005 Jul 1;121(7):977-90
pubmed: 15989949
Biochem Biophys Res Commun. 2006 Jan 6;339(1):79-88
pubmed: 16293230
Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10544-51
pubmed: 16807293
Cell Cycle. 2006 Sep;5(17):1940-5
pubmed: 16940754
Toxicol Appl Pharmacol. 2006 Dec 15;217(3):289-98
pubmed: 17078987
Science. 2007 Jul 6;317(5834):121-4
pubmed: 17615358
N Engl J Med. 2007 Nov 8;357(19):1974-6
pubmed: 17989393
J Biol Chem. 2008 Jun 20;283(25):17147-57
pubmed: 18442974
Toxicol Sci. 2009 Mar;108(1):35-47
pubmed: 19129213
Carcinogenesis. 2009 Jun;30(6):1024-31
pubmed: 19386581
Nat Rev Drug Discov. 2009 Jul;8(7):579-91
pubmed: 19478820
PLoS One. 2009 Jul 07;4(7):e6158
pubmed: 19584930
Curr Stem Cell Res Ther. 2010 Mar;5(1):74-80
pubmed: 19951255
J Biol Chem. 2010 Mar 12;285(11):8463-71
pubmed: 20061377
Free Radic Res. 2010 Apr;44(4):441-53
pubmed: 20166883
Cell. 2011 Jan 7;144(1):27-40
pubmed: 21215367
Carcinogenesis. 2011 Aug;32(8):1162-6
pubmed: 21606321
Nature. 2011 Jul 06;475(7354):106-9
pubmed: 21734707
Toxicol Sci. 2011 Oct;123(2):590-600
pubmed: 21775727
Eur J Pharmacol. 2011 Nov 30;670(2-3):333-40
pubmed: 21968144
J Transl Med. 2011 Oct 10;9:171
pubmed: 21985599
N Engl J Med. 2011 Sep 22;365(12):1118-27
pubmed: 21992124
Free Radic Biol Med. 2012 Aug 15;53(4):758-68
pubmed: 22684020
Nature. 2012 Sep 27;489(7417):519-25
pubmed: 22960745
Front Oncol. 2012 Dec 26;2:200
pubmed: 23272301
Free Radic Biol Med. 2013 Apr;57:119-31
pubmed: 23275004
Front Med. 2013 Jun;7(2):242-54
pubmed: 23681888
Free Radic Biol Med. 2013 Oct;63:369-80
pubmed: 23743293
J Biol Chem. 2014 Mar 28;289(13):8735-41
pubmed: 24515117
Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4472-7
pubmed: 24567396
Cell Signal. 2014 Jul;26(7):1604-15
pubmed: 24705025
Cancer Lett. 2014 Aug 28;351(1):64-71
pubmed: 24944078
Adv Cancer Res. 2014;122:281-320
pubmed: 24974185
Cancer Cell. 2015 Feb 9;27(2):211-22
pubmed: 25620030
Methods Mol Biol. 2015;1267:165-83
pubmed: 25636469
Nat Commun. 2015 Mar 20;6:6479
pubmed: 25790857
Lab Anim. 2015 Apr;49(1 Suppl):59-69
pubmed: 25835739
World J Hepatol. 2015 May 8;7(7):968-79
pubmed: 25954479
Antioxid Redox Signal. 2015 Oct 1;23(10):823-53
pubmed: 26058897
Redox Biol. 2015 Aug;5:347-357
pubmed: 26122399
Cell. 2016 Aug 11;166(4):963-976
pubmed: 27477511
Cancer Res. 2017 Sep 15;77(18):4797-4808
pubmed: 28655791
Cell Rep. 2017 Jun 27;19(13):2771-2781
pubmed: 28658624
Oxid Med Cell Longev. 2017;2017:8541064
pubmed: 28785378
J Biol Chem. 2017 Oct 13;292(41):16817-16824
pubmed: 28842501
Nat Med. 2017 Nov;23(11):1362-1368
pubmed: 28967920
Sci Transl Med. 2018 Feb 14;10(428):null
pubmed: 29444979
Free Radic Biol Med. 2018 Nov 1;127:248-261
pubmed: 29609022
Cell. 2018 Apr 5;173(2):321-337.e10
pubmed: 29625050
Hepatology. 2019 Apr;69(4):1768-1786
pubmed: 30561826
Carcinogenesis. 1986 Oct;7(10):1621-4
pubmed: 3757165
Proc Natl Acad Sci U S A. 1971 Apr;68(4):820-3
pubmed: 5279523
Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5258-65
pubmed: 7777494
Mol Carcinog. 1993;8(2):67-73
pubmed: 8104413
Dev Biol. 1976 Jun;50(2):249-63
pubmed: 819316
Pharmacol Ther. 1996;71(1-2):57-81
pubmed: 8910949
Biochem Biophys Res Commun. 1997 Jul 18;236(2):313-22
pubmed: 9240432