Abstract:
:Thioredoxin 1 (Trx1) is known to play an important role in protecting against cell death. However, the mechanism for control of Trx1 in cell death resulting from DNA damage has not been fully investigated. In this study, we used the DNA-damaging agent methyl methanesulfonate (MMS) to investigate the protective effects of Trx1 against DNA damage and cell death in HEK293 cells. We found that MMS application caused dose-dependent changes in the Trx1 redox state determined by redox western blotting. At lower concentrations, both reduced and oxidized Trx1 were observed, whereas the reduced band was fully oxidized at the higher concentration. Trx1 overexpression and small interfering RNA knockdown in cells revealed that reduced Trx1 after exposure to lower doses of MMS attenuated DNA damage, assessed by comet assay, and level of the DNA-damage marker histone γ-H2AX, possibly through scavenging intracellular ROS and an increase in p21 protein level via enhancing its stability. However, oxidized Trx1 lost its protective ability to DNA damage in response to higher concentration of MMS. Corresponding to the redox state control of Trx1, cell death induced by different dose of MMS was also found, by inhibiting phosphorylations of p38 and 4E-BP1. These results indicate that reduced Trx1 plays important protective roles against MMS-induced DNA damage and cell death, suggesting that cell protection is regulated by the intracellular redox state. Control of the redox state of Trx1 and its regulating proteins may offer a novel therapeutic strategy for the control of cancer.
journal_name
J Biochemjournal_title
Journal of biochemistryauthors
Gu L,Gao W,Yang HM,Wang BB,Wang XN,Xu J,Zhang Hdoi
10.1093/jb/mvv080subject
Has Abstractpub_date
2016-01-01 00:00:00pages
101-10issue
1eissn
0021-924Xissn
1756-2651pii
mvv080journal_volume
159pub_type
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journal_title:Journal of biochemistry
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pub_type: 杂志文章
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更新日期:1991-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:1998-12-01 00:00:00
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更新日期:2012-03-01 00:00:00
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journal_title:Journal of biochemistry
pub_type: 杂志文章
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更新日期:2005-06-01 00:00:00
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journal_title:Journal of biochemistry
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pub_type: 杂志文章
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更新日期:1983-02-01 00:00:00
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journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a124636
更新日期:1994-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a135582
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pub_type: 杂志文章
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更新日期:1979-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:1993-03-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of biochemistry
pub_type: 杂志文章
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journal_title:Journal of biochemistry
pub_type: 杂志文章
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更新日期:1979-06-01 00:00:00
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journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a122561
更新日期:1988-11-01 00:00:00
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journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a123050
更新日期:1990-03-01 00:00:00
abstract::Temperature and solvent effects on reaction center structures were examined in two thermophilic photosynthetic bacteria, Chloroflexus aurantiacus and Chromatium tepidum, in order to gain insight into the interactions among the reaction center proteins and pigment systems. Thermal stability of the reaction centers was ...
journal_title:Journal of biochemistry
pub_type: 杂志文章
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更新日期:1991-10-01 00:00:00
abstract::The heavy chain of myosin subfragment-1 prepared by chymotrypsin treatment had a molecular weight of about 96 K. It was split into 26 K, 50K, and 21 K fragments on trypsin treatment. The effect of actin binding on the susceptibilities of the junctions between 26 K and 50 K and between 50 K and 21 K, and on that of alk...
journal_title:Journal of biochemistry
pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a132708
更新日期:1979-12-01 00:00:00