PMID- 28785379
OWN - NLM
STAT- MEDLINE
DCOM- 20180423
LR  - 20240326
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2017
DP  - 2017
TI  - Expression of the NRF2 Target Gene NQO1 Is Enhanced in Mononuclear Cells in Human 
      Chronic Kidney Disease.
PG  - 9091879
LID - 10.1155/2017/9091879 [doi]
LID - 9091879
AB  - Reduced nuclear factor erythroid 2-related factor 2 (NRF2) pathway activity was 
      reported in models of chronic kidney disease (CKD). Pharmacological activation of 
      NRF2 is supposed to improve renal function, but data concerning the NRF2 activity 
      in human CKD are lacking. We investigated the NRF2 target NAD(P)H:quinone 
      oxidoreductase 1 (NQO1) as a readout parameter for NRF2 activity in monocytes of 
      CKD patients (n = 63) compared to those of healthy controls (n = 16). The NQO1 
      gene expression was quantified using real-time PCR and the protein content by 
      in-cell Western assays. We found a 3-4-fold increase in NQO1 gene expression in 
      CKD 1-5 (n = 29; 3.5 for NQO1/ribosomal protein L41; p < 0.001). This was 
      accompanied by a 1.1-fold increase in NQO1 protein (p = 0.06). Cardiovascular 
      disease prevalence was higher in CKD 1-5 patients with higher compared to those 
      with lower NQO1 gene expression (p = 0.02). In advanced uremia, in dialysis 
      patients (n = 34), NQO1 gene expression was less robustly upregulated than that 
      in CKD 1-5, while NQO1 protein was not upregulated. We conclude that in 
      mononuclear cells of CKD patients, the NRF2 pathway is activated by coexisting 
      pathogenic mechanisms, but in advanced uremia, the effectiveness of this 
      upregulation is reduced. Both processes could interfere with pharmacological NRF2 
      activation.
FAU - Shen, Jianlin
AU  - Shen J
AD  - Department of Orthopedics, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
AD  - Institute of Molecular Medicine, Cardiovascular and Renal Research, University of 
      Southern Denmark, Odense, Denmark.
FAU - Rasmussen, Marianne
AU  - Rasmussen M
AD  - Department of Nephrology, Odense University Hospital, Odense, Denmark.
FAU - Dong, Qi-Rong
AU  - Dong QR
AUID- ORCID: 0000-0001-8868-8003
AD  - Department of Orthopedics, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Tepel, Martin
AU  - Tepel M
AUID- ORCID: 0000-0002-0086-0997
AD  - Institute of Molecular Medicine, Cardiovascular and Renal Research, University of 
      Southern Denmark, Odense, Denmark.
AD  - Department of Nephrology, Odense University Hospital, Odense, Denmark.
FAU - Scholze, Alexandra
AU  - Scholze A
AUID- ORCID: 0000-0002-3100-8692
AD  - Department of Nephrology, Odense University Hospital, Odense, Denmark.
AD  - Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
LA  - eng
PT  - Journal Article
DEP - 20170713
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - EC 1.6.5.2 (NQO1 protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Demography
MH  - Female
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Male
MH  - Middle Aged
MH  - NAD(P)H Dehydrogenase (Quinone)/*genetics
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Renal Insufficiency, Chronic/*genetics
PMC - PMC5530440
EDAT- 2017/08/09 06:00
MHDA- 2018/04/24 06:00
PMCR- 2017/07/13
CRDT- 2017/08/09 06:00
PHST- 2017/04/07 00:00 [received]
PHST- 2017/05/03 00:00 [revised]
PHST- 2017/05/11 00:00 [accepted]
PHST- 2017/08/09 06:00 [entrez]
PHST- 2017/08/09 06:00 [pubmed]
PHST- 2018/04/24 06:00 [medline]
PHST- 2017/07/13 00:00 [pmc-release]
AID - 10.1155/2017/9091879 [doi]
PST - ppublish
SO  - Oxid Med Cell Longev. 2017;2017:9091879. doi: 10.1155/2017/9091879. Epub 2017 Jul 
      13.