Dr. Jekyll and Mr. Hyde: Oxidizable phenol-generated reactive oxygen species enhance sulforaphane's antioxidant response element activation, even as they suppress Nrf2 protein accumulation

Bauman, Bradly M.; Jeong, Chang; Savage, Matthew; Briker, Anna; Janigian, Nicholas G.; Nguyen, Ly; Kemmerer, Zachary A.; Eggler, Aimee L.

doi:10.1016/j.freeradbiomed.2018.06.039

Cited by 9 publications

(24 citation statements)

References 60 publications

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“…Many studies considered the effects of polyphenols in different systems without using specific inhibitors for critically understanding the mechanism and the real active compound responsible for the results accepted, [40,41,[43][44][45]. Several other studies, however, by introducing specific inhibitors, such as catalase, myoglobin, Peg-catalase, SOD (superoxide dismutase), Peg-SOD and MnTMPyP (manganese (III) 5,10,15,20-tetra(4-pyridylporphyrine)) [12,19,[46][47][48][49][50][51][52], identified H 2 O 2 , the active specific by-product, generated by auto-oxidation of polyphenols, affecting the physiological changes obtained. We demonstrated that catalase decreased H 2 O 2 levels generated by glucose-oxidase, but it could not cause the same effects when H 2 O 2 was generated by polyphenols [38].…”

Section: Cell Proliferation Inhibition and Progression By Polyphenolsmentioning

confidence: 99%

“…At different concentrations, they activate or inhibit the same effector [57], like HO-1 [138,139], receptor tyrosine kinase activity [92] or Nrf2 [51,58]. The activation of Nrf2 by sulforaphane was enhanced by low concentration of H 2 O 2 or polyphenols but inhibited at high concentration of the two additives, H 2 O 2 or polyphenols [51]. The oxidizable phenol 2,5-di-tert-butylhydroquinone (dtBHQ) is a useful tool for assessing H 2 O 2 contribution.…”

Section: Hormesis/eustress and Distress By Polyphenolsmentioning

confidence: 99%

“…However, only the oxidized form of tBHQ, tBQ, can act as an electrophile, since the additional tert-butyl group on dtBQ blocks its ability to react with a nucleophile [51,140]. It was found that only dtBHQ-generated H 2 O 2 is responsible for the significant enhancement of sulforaphane-induced Nrf2/ARE-regulated gene expression [51]. These results confirm our data which show that H 2 O 2 is the main molecule that activates astrocyte Nrf2 and not the quinones [13].…”

Section: Hormesis/eustress and Distress By Polyphenolsmentioning

confidence: 99%

“…Both tBHQ and dtBHQ readily oxidized to produce O 2 •− , generating H 2 O 2 either spontaneously or catalyzed by SOD3. However, only the oxidized form of tBHQ, tBQ, can act as an electrophile, since the additional tert-butyl group on dtBQ blocks its ability to react with a nucleophile [ 51 , 140 ]. It was found that only dtBHQ-generated H 2 O 2 is responsible for the significant enhancement of sulforaphane-induced Nrf2/ARE-regulated gene expression [ 51 ].…”

Section: Hormesis/eustress and Distress By Polyphenolsmentioning

confidence: 99%

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Polyphenols by Generating H2O2, Affect Cell Redox Signaling, Inhibit PTPs and Activate Nrf2 Axis for Adaptation and Cell Surviving: In Vitro, In Vivo and Human Health

Kanner

2020

Antioxidants

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Human health benefits from different polyphenols molecules consumption in the diet, derived mainly by their common activities in the gastrointestinal tract and at the level of blood micro-capillary. In the stomach, intestine and colon, polyphenols act as reducing agents preventing lipid peroxidation, generation and absorption of AGEs/ALEs (advanced glycation end products/advanced lipid oxidation end products) and postprandial oxidative stress. The low absorption of polyphenols in blood does not support their activity as antioxidants and their mechanism of activity is not fully understood. The results are from in vitro, animal and human studies, detected by relevant oxidative stress markers. The review carries evidences that polyphenols, by generating H2O2 at nM concentration, exogenous to cells and organs, act as activators of signaling factors increasing cell Eustress. When polyphenols attain high concentration in the blood system, they generate H2O2 at µM concentration, acting as cytotoxic agents and Distress. Pre-treatment of cells or organisms with polyphenols, by generating H2O2 at low levels, inhibits cellular PTPs (protein tyrosine phosphatases), inducing cell signaling through transcription of the Nrf2 (nuclear factor erythroid 2-related factor 2) axis of adaptation and protection to oxidation stress. Polyphenols ingestion at the right amount and time during the meal acts synergistically at the level of the gastrointestinal tract (GIT) and blood system, for keeping the redox homeostasis in our organism and better balancing human health.

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Section: Cell Proliferation Inhibition and Progression By Polyphenolsmentioning

confidence: 99%

Section: Hormesis/eustress and Distress By Polyphenolsmentioning

confidence: 99%

Section: Hormesis/eustress and Distress By Polyphenolsmentioning

confidence: 99%

Section: Hormesis/eustress and Distress By Polyphenolsmentioning

confidence: 99%

See 2 more Smart Citations

Polyphenols by Generating H2O2, Affect Cell Redox Signaling, Inhibit PTPs and Activate Nrf2 Axis for Adaptation and Cell Surviving: In Vitro, In Vivo and Human Health

Kanner

2020

Antioxidants

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“…This dipeptide has not yet been identified in human tissues or biofluids; thus, it is classified as an “expected” metabolite. 2,5-Di-tert-Butylhydroquinone can play an antioxidant role by producing H 2 O 2 , a source of reactive oxygen species (Rhee, 2006 ; Bauman et al, 2018 ). 2,5-di-tert-Butylhydroquinone is the oxidation substrate used to measure the catalytic activity of copper (II) enzyme-like catalysts—that is, it is a useful tool to assess reactive oxygen species contributions (Jakubiak et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

Serum and CSF Metabolites in Stroke-Free Patients Are Associated With Vascular Risk Factors and Cognitive Performance

Peng

Shen

Wang

et al. 2020

Front. Aging Neurosci.

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Background and purpose : The aggregation of vascular risk factors (VRFs) can aggravate cognitive impairment in stroke-free patients. Metabolites in serum and cerebrospinal fluid (CSF) may irreversibly reflect early functional deterioration. This study evaluated small-molecule metabolites (<1,000 Da) in the serum and CSF of patients with different degrees of cerebrovascular burden and investigated the correlation between metabolism and cognitive performance associated with VRFs. Methods : The subjects were divided into a low-risk group (10-year stroke risk ≤ 5%), a middle-risk group (10-year stroke risk >5% and <15%), and a high-risk group (10 years stroke risk ≥ 15%) according to the Framingham stroke risk profile (FSRP) score, which was used to quantify VRFs. We assess the cognitive function of the participants. We semiquantitatively quantified the small molecules using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The correlation between the small molecules and cognitive function, along with VRFs, was investigated to identify key small molecules and possible underlying metabolic pathways. Results : When the FSRP scores increased, the cognitive performances of the subjects decreased, specifically the performance regarding the tasks of immediate memory, delayed recall, and executive function. Seven metabolites (2-aminobutyric acid, Asp Asp Ser, Asp Thr Arg, Ile Cys Arg, 1-methyluric acid, 3-tert-butyladipic acid, and 5α-dihydrotestosterone glucuronide) in serum and three metabolites [Asp His, 13-HOTrE(r), and 2,5-di-tert-Butylhydroquinone] in CSF were significantly increased, and one metabolite (arachidonoyl PAF C-16) in serum was significantly decreased in high-risk group subjects. Among these metabolites, 1-methyluric acid, 3-tert-butyladipic, acid and Ile Cys Arg in serum and 13-HOTrE(r), 2,5-di-tert-butylhydroquinone, and Asp His in CSF were found to be negatively related with cognitive performance in the high-risk group. Arachidonoyl PAF C-16 in serum was found to be associated with better cognitive performance. Caffeine metabolism and the tricarboxylic acid cycle (TCA cycle) were identified as key pathways. Conclusions : 1-Methyluric acid, 3-tert-butyladipic acid, arachidonoyl PAF C-16, and Ile Cys Arg in serum and 13-HOTrE(r), 2,5-di-tert-butylhydroquinone, and Asp His in CSF were identified as potential biomarkers of vascular cognitive impairment (VCI) at the early stage. Caffeine metabolism and the TCA cycle may play important roles in the pathophysiology of VRF-associated cognitive impairment.

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Development of a “turn off–on” whole‐cell biosensor for sulforaphane detection based on the ultrasensitive activator HrpRS

Chen

et al. 2022

Biotech and App Biochem

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Sulforaphane (SFN), a defense secondary metabolite, can be used to predict the health status of plants and also has pharmacological effects, including anticancer, antioxidant, and anti‐inflammatory properties. The detection of SFN is therefore of great significance for the prevention and treatment of diseases. In this study, a “turn off” whole‐cell biosensor that can rapidly and robustly respond to the presence of SFN was constructed based on the orthogonal genetic components (hrpR, hrpS, and PhrpL) of Pseudomonas syringae (PS). The final optimized biosensor, p114(30R‐30S), was able to inhibit 91.7% of the fluorescence intensity in the presence of 100‐μM SFN. Subsequently, a HrpRS‐regulated OFF–ON genetic switch was designed by reconstituting a reverse σ70 promoter on the σ54‐PhrpL promoter sequence; this was coupled with dual‐color reporter genes to construct a “turn off–on” whole‐cell SFN biosensor. The PhrpLB variant increased the expression of green fluorescence a factor of 11.9 and reduced the expression of red fluorescence by 85.8% compared with the system in the absence of SFN. Thus, a robust switching of signal output from “turn off” to “turn on” was realized. In addition, the biosensor showed good linearity in the SFN concentration ranges of 0.1–10 μM (R2 = 0.99429) and 10–100 μM (R2 = 0.99465) and a detection limit of ~0.1 μM.

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Dr. Jekyll and Mr. Hyde: Oxidizable phenol-generated reactive oxygen species enhance sulforaphane's antioxidant response element activation, even as they suppress Nrf2 protein accumulation

Cited by 9 publications

References 60 publications

Polyphenols by Generating H2O2, Affect Cell Redox Signaling, Inhibit PTPs and Activate Nrf2 Axis for Adaptation and Cell Surviving: In Vitro, In Vivo and Human Health

Polyphenols by Generating H2O2, Affect Cell Redox Signaling, Inhibit PTPs and Activate Nrf2 Axis for Adaptation and Cell Surviving: In Vitro, In Vivo and Human Health

Serum and CSF Metabolites in Stroke-Free Patients Are Associated With Vascular Risk Factors and Cognitive Performance

Development of a “turn off–on” whole‐cell biosensor for sulforaphane detection based on the ultrasensitive activator HrpRS

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