Nrf-2 as a therapeutic target in acute kidney injury

Hejazian, Seyyedeh Mina; Khatibi, Seyed Mahdi Hosseiniyan; Soofiyani, Saiedeh Razi; Hassannejhad, Sina; Ahmadian, Elham; Ardalan, Mohammadreza; Vahed, Sepideh Zununi

doi:10.1016/j.lfs.2020.118581

Cited by 31 publications

(26 citation statements)

References 132 publications

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“…T3 can inhibit apoptosis and oxidative stress in human myocardial cells by upregulating the PKM2/PKM1 ratio. In addition, Nrf-2 regulates expression of several genes responsible for cellular detoxification, antioxidant function, anti-inflammatory effect, drug/xenobiotic transportation, and stress-related factors ( 186 ). Astrocytic DRD2 induces GSH synthesis through PKM2-mediated Nrf2 transactivation ( 187 ).…”

Section: Pkm2: a Potential Therapeutic Target Of Oxidative Stress And Inflammatory Damagementioning

confidence: 99%

Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm

Liu

Chen

et al. 2021

Front. Immunol.

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The cytokine storm is a marker of severity of various diseases and increased mortality. The altered metabolic profile and energy generation of immune cells affects their activation, exacerbating the cytokine storm. Currently, the emerging field of immunometabolism has highlighted the importance of specific metabolic pathways in immune regulation. The glycolytic enzyme pyruvate kinase M2 (PKM2) is a key regulator of immunometabolism and bridges metabolic and inflammatory dysfunction. This enzyme changes its conformation thus walks in different fields including metabolism and inflammation and associates with various transcription factors. This review summarizes the vital role of PKM2 in mediating immunometabolic reprogramming and its role in inducing cytokine storm, with a focus on providing references for further understanding of its pathological functions and for proposing new targets for the treatment of related diseases.

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Section: Pkm2: a Potential Therapeutic Target Of Oxidative Stress And Inflammatory Damagementioning

confidence: 99%

Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm

Liu

Chen

et al. 2021

Front. Immunol.

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“…In one of the studies, the expression of Nrf2-target genes was found to be induced instantly after IRI (and consequent oxidative stress) and returned to basal levels within 24 h [ 53 ]. Additionally, in Keap1 gene-deleted mice, tubular epithelial cells were found to be responsible for the Nrf2-mediated renoprotection under oxidative stress [ 55 , 56 , 57 ], and the severity of renal IRI is accentuated both in the murine model [ 58 ] and the Nrf2-knockout mice model [ 59 ]. Furthermore, T cell-specific activation of Nrf2 is reported to be renoprotective in I/R-induced acute kidney injury in mice [ 60 ].…”

Section: Role Of Nrf2/keap1/are Pathway In Irimentioning

confidence: 99%

Pharmacological Protection against Ischemia-Reperfusion Injury by Regulating the Nrf2-Keap1-ARE Signaling Pathway

Uçar

Saha³

et al. 2021

Antioxidants

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Ischemia/reperfusion (I/R) injury is associated with substantial clinical implications, including a wide range of organs such as the brain, kidneys, lungs, heart, and many others. I/R injury (IRI) occurs due to the tissue injury following the reestablishment of blood supply to ischemic tissues, leading to enhanced aseptic inflammation and stimulation of oxidative stress via reactive oxygen and nitrogen species (ROS/RNS). Since ROS causes membrane lipids’ peroxidation, triggers loss of membrane integrity, denaturation of proteins, DNA damage, and cell death, oxidative stress plays a critical part in I/R pathogenesis. Therefore, ROS regulation could be a promising therapeutic strategy for IRI. In this context, Nrf2 (NF-E2-related factor 2) is a transcription factor that regulates the expression of several factors involved in the cellular defense against oxidative stress and inflammation, including heme oxygenase-1 (HO-1). Numerous studies have shown the potential role of the Nrf2/HO-1 pathway in IRI; thus, we will review the molecular aspects of Nrf2/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response element (ARE) signaling pathway in I/R, and we will also highlight the recent insights into targeting this pathway as a promising therapeutic strategy for preventing IRI.

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“…One such potential therapeutic strategy involves targeting endogenous ROS to stabilize the microenvironment and thereby ameliorate pathophysiological effects. Among various antioxidative pathways, the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway includes a key cytoprotective transcription factor that functions in the amelioration of various oxidative stress-and inflammation-associated diseases [18,19]. Once released, Nrf2 moves into the cell nucleus and binds to the DNA at the location of the antioxidant response elements to enhance the expression of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase, during oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

et al. 2021

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Inflammation and oxidative stress are closely related processes in the pathogenesis of various ocular diseases. Uveitis is a disorder of the uvea and ocular tissues that causes extreme pain, decreases visual acuity, and can eventually lead to blindness. The pharmacological functions of fucoxanthin, isolated from brown algae, induce a variety of therapeutic effects such as oxidative stress reduction and repression of inflammation reactions. However, the specific anti-inflammatory effects of fucoxanthin on pathogen-associated molecular pattern (PAMP) lipopolysaccharide-induced uveitis have yet to be extensively described. Therefore, the aim of present study was to investigate the anti-inflammatory effects of fucoxanthin on uveitis in rats. The results showed that fucoxanthin effectively enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in ocular tissues. Furthermore, fucoxanthin significantly increased the ocular activities of superoxide dismutase and decreased the levels of malondialdehyde stimulated by PAMP-induced uveitis. Ocular hypertension and the levels of inflammatory cells and proinflammatory cytokine tumor necrosis factor-alpha in the aqueous humor were alleviated with fucoxanthin treatment. Consequently, compared to the observed effects in lipopolysaccharide groups, fucoxanthin treatment significantly preserved iris sphincter innervation and pupillary function. Additionally, PAMP-induced corneal endothelial disruption was significantly inhibited by fucoxanthin treatment. Overall, these findings suggest that fucoxanthin may protect against inflammation from PAMP-induced uveitis by promoting the Nrf2 pathway and inhibiting oxidative stress.

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Nrf-2 as a therapeutic target in acute kidney injury

Cited by 31 publications

References 132 publications

Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm

Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm

Pharmacological Protection against Ischemia-Reperfusion Injury by Regulating the Nrf2-Keap1-ARE Signaling Pathway

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

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