PMID- 29423025
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 3
DP  - 2018 Jan 9
TI  - Methylseleninic acid induces NAD(P)H:quinone oxidoreductase-1 expression through 
      activation of NF-E2-related factor 2 in Chang liver cells.
PG  - 3014-3028
LID - 10.18632/oncotarget.10289 [doi]
AB  - Selenium has been reported to induce the expression of some cytoprotective 
      enzymes, which may account for its chemoprotective and chemopreventive effects. 
      However, it remains largely unresolved whether these effects are exerted by 
      selenium itself or mediated by its metabolite(s). In the present study, 
      methylseleninic acid (MSeA), a monomethylated selenium, induced the expression of 
      NAD(P)H:quinone oxidoreductase-1 (NQO-1) in human Chang liver cells. Expression 
      of NQO-1 and other antioxidant/stress response genes is primarily regulated by 
      the transcription factor NF-E2-related factor2 (Nrf2). Exposure of human Chang 
      liver cells to MSeA (3 muM) increased nuclear translocation of Nrf2 and binding to 
      antioxidant response elements. Silencing Nrf2 markedly reduced the MSeA-induced 
      NQO-1 expression. In comparison with embryonic fibroblasts from Nrf2 wild-type 
      mice, those from Nrf2 knockout mice failed to induce NQO-1 expression when 
      treated with MSeA. Moreover, MSeA treatment enhanced ubiquitination of Keap1, but 
      repressed Nrf2 ubiquitination. Pretreatment of cells with dithiothreitol 
      abrogated the MSeA-induced NQO-1 expression, suggesting that MSeA causes Keap1 
      thiol modification. MSeA-induced NQO-1 upregulation was attenuated in cells 
      harbouring the mutant Keap1 in which the cysteine 151 residue was replaced by 
      serine. Oral administration of MSeA (1 mg/kg) by gavage to mice induced hepatic 
      NQO-1 expression. Similar to MSeA, methylselenol generated from selenomethionine 
      by methioninase activity induced NQO-1 expression. In conclusion, MSeA, the 
      immediate precursor of methylselenol, upregulates the expression of NQO-1 via the 
      Keap1-Nrf2 signaling. The above findings suggest that biological activities of 
      selenium are dependent on the nature of the metabolites as well as the type of 
      ingested selenium formulations.
FAU - Park, Jong-Min
AU  - Park JM
AD  - Tumor Microenvironment Global Core Research Center and Research Institute of 
      Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
FAU - Kim, Do-Hee
AU  - Kim DH
AD  - Tumor Microenvironment Global Core Research Center and Research Institute of 
      Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
FAU - Na, Hye-Kyung
AU  - Na HK
AD  - Department of Food and Nutrition, College of Human Ecology, Sungshin Women's 
      University, Seoul, South Korea.
FAU - Surh, Young-Joon
AU  - Surh YJ
AD  - Tumor Microenvironment Global Core Research Center and Research Institute of 
      Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
AD  - Cancer Research Institute, Seoul National University, Seoul, South Korea.
LA  - eng
GR  - 27302C0138/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20160625
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5790442
OTO - NOTNLM
OT  - Nrf2
OT  - chemoprevention
OT  - methylseleninic acid
OT  - selenium
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2016/06/25 00:00
MHDA- 2016/06/25 00:01
PMCR- 2018/01/09
CRDT- 2018/02/10 06:00
PHST- 2015/11/01 00:00 [received]
PHST- 2016/05/06 00:00 [accepted]
PHST- 2018/02/10 06:00 [entrez]
PHST- 2016/06/25 00:00 [pubmed]
PHST- 2016/06/25 00:01 [medline]
PHST- 2018/01/09 00:00 [pmc-release]
AID - 10289 [pii]
AID - 10.18632/oncotarget.10289 [doi]
PST - epublish
SO  - Oncotarget. 2016 Jun 25;9(3):3014-3028. doi: 10.18632/oncotarget.10289. 
      eCollection 2018 Jan 9.