Methionine sulfoxide reductase A protects hepatocytes against acetaminophen-induced toxicity via regulation of thioredoxin reductase 1 expression

Singh, Mahendra Pratap; Kwak, Geun-Hee; Kim, Ki Young; Kim, Hwa-Young

doi:10.1016/j.bbrc.2017.04.119

Cited by 14 publications

(12 citation statements)

References 25 publications

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Section: Resultsmentioning

confidence: 99%

“…Depletion of TXNRD1 induces resistance to APAP-induced toxicity in livers and hepatocytes [22,28,29]. We recently reported that MsrA can modulate hepatic TXNRD1 expression upon APAP challenge [22]. MsrA deficiency increased APAP-induced TXNRD1 expression levels in hepatocytes, whereas overexpression of MsrA reduced the elevated TXNRD1 levels in APAP-treated MsrA-deficient cells [22].…”

Section: Resultsmentioning

confidence: 99%

“…We recently reported that MsrA can modulate hepatic TXNRD1 expression upon APAP challenge [22]. MsrA deficiency increased APAP-induced TXNRD1 expression levels in hepatocytes, whereas overexpression of MsrA reduced the elevated TXNRD1 levels in APAP-treated MsrA-deficient cells [22]. Therefore, we tested whether MsrB1 deficiency would affect the expression of hepatic TXNRD1 under APAP conditions.…”

Section: Resultsmentioning

confidence: 99%

“…Primary hepatocytes were isolated from the livers of male MsrB1 +/+ and MsrB1 −/− mice (8–10 weeks old) using a two-step collagenase perfusion method, as previously described [21,22]. Isolated cells were seeded onto culture plates in DMEM supplemented with 10 % fetal bovine serum, 100 U penicillin/streptomycin, and 3.2 mg/L insulin.…”

Section: Methodsmentioning

confidence: 99%

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Selenoprotein MsrB1 deficiency exacerbates acetaminophen-induced hepatotoxicity via increased oxidative damage

Kim

Kwak

Singh

et al. 2017

Archives of Biochemistry and Biophysics

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Acetaminophen (APAP) overdose induces acute liver damage and failure via reactive oxygen species production and glutathione (GSH) depletion. Methionine sulfoxide reductase B1 (MsrB1) is an antioxidant selenoenzyme that specifically catalyzes the reduction of methionine R-sulfoxide residues. In this study, we used MsrB1 gene-knockout mice and primary hepatocytes to investigate the effect of MsrB1 on APAP-induced hepatotoxicity. Analyses of histological alterations and serum indicators of liver damage showed that MsrB1−/− mice were more susceptible to APAP-induced acute liver injury than wild-type (MsrB1+/+) mice. Consistent with the in vivo results, primary MsrB1−/− hepatocytes displayed higher susceptibility to APAP-induced cytotoxicity than MsrB1+/+ cells. MsrB1 deficiency increased hepatic oxidative stress after APAP challenge such as hydrogen peroxide production, lipid peroxidation, and protein oxidation levels. Additionally, basal and APAP-induced ratios of reduced-to-oxidized GSH (GSH/GSSG) were significantly lower in MsrB1−/− than in MsrB1+/+ livers. Nrf2 nuclear accumulation and heme oxygenase-1 expression levels after APAP challenge were lower in MsrB1−/− than in MsrB1+/+ livers, suggesting that MsrB1 deficiency attenuates the APAP-induced activation of Nrf2. Collectively, the results of this study suggest that selenoprotein MsrB1 plays a protective role against APAP-induced hepatotoxicity via its antioxidative function.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Selenoprotein MsrB1 deficiency exacerbates acetaminophen-induced hepatotoxicity via increased oxidative damage

Kim

Kwak

Singh

et al. 2017

Archives of Biochemistry and Biophysics

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“…After generation of null-hepatocytes for both TrxR and GSH reductase genes in transgenic mice, though they were long-term viable, these mice were dependent on methionine supplementation in their diets needed for de novo synthesis of cysteine and GSH [21] . There are other reductases capable of redox-regulation of the system, but the methionine sulfoxide pathway is responsible for maintaining the redox environment when NADPH does not deliver the reducing power either to Trx or to GSH [22] , [23] , [24] .…”

Section: Thioredoxin-1 In the Context Of The Thioredoxin Systemmentioning

confidence: 99%

Thioredoxin promotes survival signaling events under nitrosative/oxidative stress associated with cancer development

2017

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Accumulating mutations may drive cells into the acquisition of abnormal phenotypes that are characteristic of cancer cells. Cancer cells feature profound alterations in proliferation programs that result in a new population of cells that overrides normal tissue construction and maintenance programs. To achieve this goal, cancer cells are endowed with up regulated survival signaling pathways. They also must counteract the cytotoxic effects of high levels of nitric oxide (NO) and of reactive oxygen species (ROS), which are by products of cancer cell growth. Accumulating experimental evidence associates cancer cell survival with their capacity to up-regulate antioxidant systems. Elevated expression of the antioxidant protein thioredoxin-1 (Trx1) has been correlated with cancer development. Trx1 has been characterized as a multifunctional protein, playing different roles in different cell compartments. Trx1 migrates to the nucleus in cells exposed to nitrosative/oxidative stress conditions. Trx1 nuclear migration has been related to the activation of transcription factors associated with cell survival and cell proliferation. There is a direct association between the p21Ras-ERK1/2 MAP Kinases survival signaling pathway and Trx1 nuclear migration under nitrosative stress. The expression of the cytoplasmic protein, the thioredoxin-interacting protein (Txnip), determines the change in Trx1 cellular compartmentalization. The anti-apoptotic actions of Trx1 and its denitrosylase activity occur in the cytoplasm and serve as important regulators of cell survival. Within this context, this review focuses on the participation of Trx1 in cells under nitrosative/oxidative stress in survival signaling pathways associated with cancer development.

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Methionine sulfoxide and the methionine sulfoxide reductase system as modulators of signal transduction pathways: a review

Moskovitz

Smith

2021

Amino Acids

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Methionine sulfoxide reductase A protects hepatocytes against acetaminophen-induced toxicity via regulation of thioredoxin reductase 1 expression

Cited by 14 publications

References 25 publications

Selenoprotein MsrB1 deficiency exacerbates acetaminophen-induced hepatotoxicity via increased oxidative damage

Selenoprotein MsrB1 deficiency exacerbates acetaminophen-induced hepatotoxicity via increased oxidative damage

Thioredoxin promotes survival signaling events under nitrosative/oxidative stress associated with cancer development

Methionine sulfoxide and the methionine sulfoxide reductase system as modulators of signal transduction pathways: a review

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