MicroRNA-mediated regulation of Nrf2 signaling pathway: Implications in disease therapy and protection against oxidative stress

Ashrafizadeh, Milad; Ahmadi, Zahra; Samarghandian, Saeed; Mohammadinejad, Reza; Yaribeygi, Habib; Sathyapalan, Thozhukat; Sahebkar, Amirhossein

doi:10.1016/j.lfs.2020.117329

Cited by 48 publications

(37 citation statements)

References 141 publications

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“…Under physiological conditions, the NRF2 expression level is low; however, it can be induced significantly under the influence of factors causing oxidative stress, such as poisoning, volatility, hyperglycemia, and hypoxia [53,54]. Our observations are consistent with the classical pattern of NRF2 activation [50]. In addition, the level of NRF2 in the cytoplasm was significantly downregulated after OTA treatment, and the level of NRF2 in the cytoplasm was even lower after ASX pretreatment.…”

Section: Discussionsupporting

confidence: 87%

“…NRF2 is an important transcriptional activator of antioxidant genes and is important in antioxidant protection [49]. After activation of the NRF2 signaling pathway, it contributes to the expression of a series of downstream antioxidant proteins, such as NQO1, HO-1, γ-GCS, and GSH-Px [50]. Previous studies have also shown that grape seed proanthocyanidins reduce the cytotoxicity of cisplatin-induced human embryonic kidney cells by regulating NRF2/HO-1 in vitro [51].…”

Section: Discussionmentioning

confidence: 99%

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Protective Effect of Astaxanthin on Ochratoxin A-Induced Kidney Injury to Mice by Regulating Oxidative Stress-Related NRF2/KEAP1 Pathway

et al. 2020

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The present study aimed to investigate the effects of astaxanthin (ASX) on ochratoxin A (OTA)-induced renal oxidative stress and its mechanism of action. Serum kidney markers, histomorphology, ultrastructural observation, and oxidative stress indicators were assessed. Meanwhile, quantitative real-time reverse transcription PCR and western blotting detection of NRF2 (encoding nuclear factor, erythroid 2 like) and members of the NRF2/KEAP1 signaling pathway (KEAP1 (encoding Kelch-like ECH-associated protein), NQO1 (encoding NAD(P)H quinone dehydrogenase), HO-1 (encoding heme oxygenase 1), γ-GCS (gamma-glutamylcysteine synthetase), and GSH-Px (glutathione peroxidase 1)) were performed. Compared with the control group, the OTA-treated group showed significantly increased levels of serum UA (uric acid) and BUN (blood urea nitrogen), tubular epithelial cells were swollen and degenerated, and the levels of antioxidant enzymes decreased significantly, and the expression of NRF2 (cytoplasm), NQO1, HO-1, γ-GCS, and GSH-Px decreased significantly. More importantly, after ASX pretreatment, compared with the OTA group, serum markers were decreased, epithelial cells appeared normal; the expression of antioxidant enzymes increased significantly, NQO1, HO-1, γ-GCS and GSH-Px levels increased significantly, and ASX promoted the transfer of NRF2 from the cytoplasm to the nucleus. These results highlight the protective ability of ASX in renal injury caused by OTA exposure, and provide theoretical support for ASX’s role in other mycotoxin-induced damage.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Protective Effect of Astaxanthin on Ochratoxin A-Induced Kidney Injury to Mice by Regulating Oxidative Stress-Related NRF2/KEAP1 Pathway

et al. 2020

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“…miRs, such as miR-144, miR-28, and miR-93, diminish the Nrf2 signaling pathway via various mechanisms [ 149 , 150 , 151 ], whereas miR-200a and miR-7 activate Nrf2 signaling pathway by targeting keap1 [ 151 , 152 ]. There is a comprehensive review on miR-mediated regulation of Nrf2 activity [ 153 ].…”

Section: Discussionmentioning

confidence: 99%

Natural Nrf2 Modulators for Skin Protection

Boo

2020

Antioxidants

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Since the discovery of antioxidant responsive elements (ARE), which are commonly found in the promoter of the Phase II metabolism/antioxidant enzymes, and nuclear factor erythroid 2-related factor 2 (Nrf2), the transcription factor that binds to ARE, the study conducted in this field has expanded remarkably over the decades, and the Nrf2-mediated pathway is now recognized to occupy a central position in cell defense mechanisms. Induction of the Phase II metabolism/antioxidant enzymes through direct activation of Nrf2 can be a promising strategy for preventing degenerative diseases in general, but a dark side of this strategy should be considered, as Nrf2 activation can enhance the survival of cancer cells. In this review, we discuss the historical discovery of Nrf2 and the regulatory mechanism of the Nrf2-mediated pathway, focusing on the interacting proteins and post-translational modifications. In addition, we discuss the latest studies that examined various natural Nrf2 modulators for the protective roles in the skin, in consideration of their dermatological and cosmetic applications. Studies are reviewed in the order of time of research as much as possible, to help understand how and why such studies were conducted under the circumstances of that time. We hope that this review can serve as a steppingstone in conducting more advanced research by providing a scientific basis for researchers newly entering this field.

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“…The contribution of miRNAs to the regulation of NRF2 signaling is widely recognized. For example, downregulation by targeting the 3 untranslated region (3 UTR) "seed" sequences in NFE2L2 mRNA has been reported for miR-153, miR142-5p, mi-R27a, miR-144, miR34a, and miR-93 (reviewed in [48,49]). On the other hand, an increase in NRF2 expression and activity was observed by miRNAs targeting the 3 UTR of KEAP1 mRNA.…”

Section: Regulation By Non-coding Rnasmentioning

confidence: 99%

Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals

Bhattacharjee

Dashwood

2020

Antioxidants

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Epigenetics has provided a new dimension to our understanding of nuclear factor erythroid 2–related factor 2/Kelch-like ECH-associated protein 1 (human NRF2/KEAP1 and murine Nrf2/Keap1) signaling. Unlike the genetic changes affecting DNA sequence, the reversible nature of epigenetic alterations provides an attractive avenue for cancer interception. Thus, targeting epigenetic mechanisms in the corresponding signaling networks represents an enticing strategy for therapeutic intervention with dietary phytochemicals acting at transcriptional, post-transcriptional, and post-translational levels. This regulation involves the interplay of histone modifications and DNA methylation states in the human NFE2L2/KEAP1 and murine Nfe2l2/Keap1 genes, acetylation of lysine residues in NRF2 and Nrf2, interaction with bromodomain and extraterminal domain (BET) acetyl “reader” proteins, and non-coding RNAs such as microRNA (miRNA) and long non-coding RNA (lncRNA). Phytochemicals documented to modulate NRF2 signaling act by reversing hypermethylated states in the CpG islands of NFE2L2 or Nfe2l2, via the inhibition of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), through the induction of ten-eleven translocation (TET) enzymes, or by inducing miRNA to target the 3′-UTR of the corresponding mRNA transcripts. To date, fewer than twenty phytochemicals have been reported as NRF2 epigenetic modifiers, including curcumin, sulforaphane, resveratrol, reserpine, and ursolic acid. This opens avenues for exploring additional dietary phytochemicals that regulate the human epigenome, and the potential for novel strategies to target NRF2 signaling with a view to beneficial interception of cancer and other chronic diseases.

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MicroRNA-mediated regulation of Nrf2 signaling pathway: Implications in disease therapy and protection against oxidative stress

Cited by 48 publications

References 141 publications

Protective Effect of Astaxanthin on Ochratoxin A-Induced Kidney Injury to Mice by Regulating Oxidative Stress-Related NRF2/KEAP1 Pathway

Protective Effect of Astaxanthin on Ochratoxin A-Induced Kidney Injury to Mice by Regulating Oxidative Stress-Related NRF2/KEAP1 Pathway

Natural Nrf2 Modulators for Skin Protection

Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals

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