Expression of the NRF2 Target Gene NQO1 Is Enhanced in Mononuclear Cells in Human Chronic Kidney Disease
Autor: | Martin Tepel, Alexandra Scholze, Qi-Rong Dong, Marianne H. Rasmussen, Jianlin Shen |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Aging medicine.medical_specialty Article Subject Renal function Biology urologic and male genital diseases Biochemistry Peripheral blood mononuclear cell 03 medical and health sciences Downregulation and upregulation Internal medicine Gene expression Journal Article medicine lcsh:QH573-671 Regulation of gene expression lcsh:Cytology Cell Biology General Medicine medicine.disease Uremia 030104 developmental biology Endocrinology NAD+ kinase Kidney disease |
Zdroj: | Oxidative Medicine and Cellular Longevity, Vol 2017 (2017) Shen, J, Rasmussen, M, Dong, Q-R, Tepel, M & Scholze, A 2017, ' Expression of the NRF2 Target Gene NQO1 Is Enhanced in Mononuclear Cells in Human Chronic Kidney Disease ', Oxidative Medicine and Cellular Longevity, vol. 2017, 9091879 . https://doi.org/10.1155/2017/9091879 |
ISSN: | 1942-0994 1942-0900 |
Popis: | 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. |
Databáze: | OpenAIRE |
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