Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission

O'Mealey, Gary B.; Berry, William L.; Plafker, Scott M.

doi:10.1016/j.redox.2016.11.007

Cited by 57 publications

(40 citation statements)

References 57 publications

(65 reference statements)

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“…Moreover, sulforaphane exerted protection of ARPE-19 cell line exposed to 400 μM H 2 O 2 by up-regulating the translation of thioredoxin and Nrf2 ( Tanito et al, 2005 ) and has been suggested to promote regeneration of retinal cells ( Dulull et al, 2018 ). Recently the protective effect of sulforaphane on RPE cells was correlated with preventing mitochondrial fission independently of Nrf2 activation ( O’Mealey et al, 2017 ).…”

Section: Nrf2 Activating Compounds In Amd Therapymentioning

confidence: 99%

Oxidative Stress in Age-Related Macular Degeneration: Nrf2 as Therapeutic Target

2018

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Age-related macular degeneration is one of the leading causes of vision loss in the elderly. Genetics, environmental insults, and age-related issues are risk factors for the development of the disease. All these risk factors are linked to the induction of oxidative stress. In young subjects retinal pigment epithelial cells mitigate reactive oxygen generation by the elimination of dysfunctional mitochondria, via mitophagy, and by increasing antioxidant defenses via Nrf2 activation. The high amount of UV light absorbed by the retina, together with cigarette smoking, cooperate with the aging process to increase the amount of reactive oxygen species generated by retinal pigment epithelium where oxidative stress arises. Moreover, in the elderly both the mitophagic process and Nrf2 activation are impaired thus causing retinal cell death. This review will focus on the impact of oxidative stress on the pathogenesis of age-related macular degeneration and analyze the natural and synthetic Nrf2-activating compounds that have been tested as potential therapeutic agents for the disease.

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Section: Nrf2 Activating Compounds In Amd Therapymentioning

confidence: 99%

Oxidative Stress in Age-Related Macular Degeneration: Nrf2 as Therapeutic Target

2018

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“…Plausible mechanisms of cancer drug resistance. The mechanisms can generally be classified as pharmacological and cellular physiological mechanisms, which either feed into or feed out of the well-known and characterised hallmarks of cancer [12] Epidermoid cancer, Prostate cancer Cisplatin [39] TFs: transcription factors second domain, known as Neh2 [ Figure 2], possesses two essential motifs known as DLG, which has less affinity for Kelch-like ECH-associated protein 1 (KEAP1), and ETGE, which has a high affinity for the interaction between NRF2 and KEAP1 [51,52] . The Neh3 domain contains a carboxy-terminal which associates with transcription co-activators such as chromodomain helicase DNA binding protein 6, which is responsible for the transactivation of ARE-dependent genes.…”

Section: Nrf2 and Its Functionmentioning

confidence: 99%

Emerging role of nuclear factor erythroid 2-related factor 2 in the mechanism of action and resistance to anticancer therapies

Paramasivan¹,

Kankia²,

Langdon³

et al. 2019

CDR

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Nuclear factor E2-related factor 2 (NRF2), a transcription factor, is a master regulator of an array of genes related to oxidative and electrophilic stress that promote and maintain redox homeostasis. NRF2 function is well studied in in vitro, animal and general physiology models. However, emerging data has uncovered novel functionality of this transcription factor in human diseases such as cancer, autism, anxiety disorders and diabetes. A key finding in these emerging roles has been its constitutive upregulation in multiple cancers promoting pro-survival phenotypes. The survivability pathways in these studies were mostly explained by classical NRF2 activation involving KEAP-1 relief and transcriptional induction of reactive oxygen species (ROS) neutralizing and cytoprotective drug-metabolizing enzymes (phase I, II, III and 0). Further, NRF2 status and activation is associated with lowered cancer therapeutic efficacy and the eventual emergence of therapeutic resistance. Interestingly, we and others have provided further evidence of direct NRF2 regulation of anticancer drug targets like receptor tyrosine kinases and DNA damage and repair proteins and kinases with implications for therapy outcome. This novel finding demonstrates a renewed role of NRF2 as a key modulatory factor informing anticancer therapeutic outcomes, which extends beyond its described classical role as a ROS regulator. This review will provide a knowledge base for these emerging roles of NRF2 in anticancer therapies involving feedback and feed forward models and will consolidate and present such findings in a systematic manner. This places NRF2 as a key determinant of action, effectiveness and resistance to anticancer therapy.

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“…The past decade has seen increasing interest in the potential health and medicinal benefits of naturally occurring antioxidants. Specifically, the health benefits of cruciferous vegetables have been identified by epidemiological studies [1][2][3], stimulating the identification of the likely active antioxidant components of these food groups. For example, resveratrol [4][5][6], vitamins C [7] and E [8], and selenium [9] have all been studied for their antioxidant therapeutic potential.…”

Section: Introductionmentioning

confidence: 99%

Measuring Sulforaphane and Its Metabolites in Human Plasma: A High Throughput Method

et al. 2020

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(1) Background: There is increasing understanding of the potential health benefits of cruciferous vegetables. In particular sulforaphane (SFN), found in broccoli, and its metabolites sulforaphane-glutathione (SFN-GSH), sulforaphane-cysteine (SFN-Cys), sulforaphane cysteine-glycine (SFN-CG) and sulforaphane-N-acetyl-cysteine (SFN-NAC) have potent antioxidant effects that may offer therapeutic value. Clinical investigation of sulforaphane as a therapeutic antioxidant requires a sensitive and high throughput process for quantification of sulforaphane and metabolites; (2) Methods: We collected plasma samples from healthy human volunteers before and for eight hours after consumption of a commercial broccoli extract supplement rich in sulforaphane. A rapid and sensitive method for quantification of sulforaphane and its metabolites in human plasma using Liquid Chromatography–Mass Spectrometry (LC–MS) has been developed; (3) Results: The LC–MS analytical method was validated at concentrations ranging between 3.9 nM and 1000 nM for SFN-GSH, SFN-CG, SFN-Cys and SFN-NAC and between 7.8 nM and 1000 nM in human plasma for SFN. The method displayed good accuracy (1.85%–14.8% bias) and reproducibility (below 9.53 %RSD) including low concentrations 3.9 nM and 7.8 nM. Four SFN metabolites quantitation was achieved using external standard calibration and in SFN quantitation, SFN-d8 internal standardization was used. The reported method can accurately quantify sulforaphane and its metabolites at low concentrations in plasma; (4) Conclusions: We have established a time- and cost-efficient method of measuring sulforaphane and its metabolites in human plasma suitable for high throughput application to clinical trials.

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Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission

Cited by 57 publications

References 57 publications

Oxidative Stress in Age-Related Macular Degeneration: Nrf2 as Therapeutic Target

Oxidative Stress in Age-Related Macular Degeneration: Nrf2 as Therapeutic Target

Emerging role of nuclear factor erythroid 2-related factor 2 in the mechanism of action and resistance to anticancer therapies

Measuring Sulforaphane and Its Metabolites in Human Plasma: A High Throughput Method

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