Upregulation of phase II enzymes through phytochemical activation of Nrf2 protects cardiomyocytes against oxidant stress

Reuland, Danielle J.; Khademi, Shadi; Castle, Christopher J.; Irwin, David; McCord, Joe M.; Miller, Benjamin F.; Hamilton, Karyn L.

doi:10.1016/j.freeradbiomed.2012.11.016

Cited by 90 publications

(62 citation statements)

References 50 publications

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“…Therefore, we used a comparatively low dosage of tBHQ (1 mg/kg) to avoid such severe effects. Recently, several Nrf2 activators, including sulforaphane and bardoxolone and many medicinal plants mixtures (Bai et al, 2013;Reuland et al, 2013;Ruiz et al, 2013), have been reported to protect cardiomyocytes against high glucose or oxidative stress. However, additional studies are required to determine whether consistent results can be obtained from either an ATF3 inducer or an Nrf2 activator after pressure overload-induced heart failure.…”

Section: Atf3 Regulates Cardiac Hypertrophymentioning

confidence: 99%

Activating Transcription Factor 3 Protects against Pressure-Overload Heart Failure via the Autophagy Molecule Beclin-1 Pathway

Lin

Chen

et al. 2014

Mol Pharmacol

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Activating transcription factor 3 (ATF3), a cAMP response element-binding protein/ATF family transcription factors member, has been implicated in the cardiovascular and inflammatory system and is rapidly induced by ischemic-reperfusion injuries. We performed transverse aortic banding (TAB) experiments using ATF3 gene-deleted mice (ATF3 2/2 ) and wild-type (WT) mice to determine what effect it might have on heart failure induced by pressure overloading. Compared with the WT mice, ATF3 2/2 mice were found by echocardiography to have decreased left ventricular contractility with loss of normal cardiac hypertrophic remodeling. The ATF3 2/2 mice had greater numbers of terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling-positive cells and higher levels of activated caspase-3, as well as more apoptosis. Restoration of ATF3 expression in the heart of ATF3 2/2 mice by adenovirus-induced ATF3 treatment significantly improved cardiac contractility after TAB. The results from molecular and biochemical analyses, including chromatin immune-precipitation and in vitro /in vivo promoter assays, showed that ATF3 bound to the ATF/cAMP response element of the Beclin-1 promoter and that ATF3 reduced autophagy via suppression of the Beclin-1-dependent pathway. Furthermore, infusion of tert-butylhydroquinone (tBHQ), a selective ATF3 inducer, increased the expression of ATF3 via the nuclear factor erythroid 2-related transcriptional factor, inhibited TABinduced cardiac dilatation, and increased left ventricular contractility, thereby rescuing heart failure. Our study identified a new epigenetic regulation mediated by the stress-inducible gene ATF3 on TAB-induced cardiac dysfunction. These findings suggest that the ATF3 activator tBHQ may have therapeutic potential for the treatment of pressure-overload heart failure induced by chronic hypertension or other pressure overload mechanisms.

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Section: Atf3 Regulates Cardiac Hypertrophymentioning

confidence: 99%

Activating Transcription Factor 3 Protects against Pressure-Overload Heart Failure via the Autophagy Molecule Beclin-1 Pathway

Lin

Chen

et al. 2014

Mol Pharmacol

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“…Nuclear factor kappa-B (NF-B) is an important transcription factor present in macrophages and leads to the transcription of pro-inflammatory cytokines, while nuclear factor (erythroidderived 2)-like 2 (Nrf2) is a transcriptional regulator of phase II antioxidant enzymes and its activation has been suggested to be an important step in attenuating oxidative stress associated with cardiovascular diseases (Reuland et al, 2012). NF-B was expectedly and consistently upregulated in the M1 population and downregulated in M2a compared with RMs (Figure 2A), and the exposure to naringenin and its phase II metabolites did not affect this trend significantly.…”

Section: Resultsmentioning

confidence: 99%

Effects of naringenin and its phase II metabolites onin vitrohuman macrophage gene expression

Dall’Asta

Derlindati

Curella

et al. 2013

International Journal of Food Sciences and Nutrition

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Naringenin, together with its glycosidic forms, is a flavanone abundant in grapefruit and orange. It has been detected in human plasma, following citrus juice intake, at sub-µmolar concentrations, and its main phase II conjugated metabolites (naringenin-7-O-glucuronide and narigenin-4'-O-glucuronide) have been identified in urine. Recent evidence suggests a potential active anti-inflammatory role of flavonoids on macrophages, cells actively involved in atherogenesis. The aim of this study was to evaluate the effects of naringenin and its phase II metabolites on the expression of specific genes in differently activated macrophages at concentrations coherent with dietary exposure. Results suggest that phase II metabolites, as well as the aglyconic form of naringenin, were able to perturb macrophage gene expression in directions that are not always consistent with anti-inflammatory effects. Moreover, the effects of metabolites were not always consistent with each other and with those of their aglycone, underlining the paramount importance of testing physiological forms of phytochemicals within in vitro experimental models. In vivo studies are needed to further explore these observations and investigate their practical consequences.

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“…The most quoted cancer prevention mechanism is via their activity, elicited either through direct free radical absorption or through induction od antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione via a variety of molecular mechanisms [77,78].…”

Section: Discussionmentioning

confidence: 99%

In vivo antitumor potential of extracts from different parts of Bauhinia variegata linn. Against b16f10 melanoma tumour model in c57bl/6 mice

Pandey

2017

Appl Cancer Res

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Background: Melanoma is a metastatic type of skin cancer that is difficult to treat and the majority of efforts are directed to the design of new drugs. Medicinal Plants have been the primary source of medicines since life on earth; more than 50% of existing cancer treatments is derived from plants. Bauhinia variegata is well-known medicinal plant used from the ancient era to till date for their medicinal values. Scientific literatures have not documented any evidence of the antitumour potential of Bauhinia variegata against B16F10 melanoma tumor model in C57BL mice. The present investigation was undertaken to explore the antitumour activity of Leaf, stem bark and flower extract of Bauhinia variegata against B16F10 melanoma tumour model in C57BL mice. Methods: Hydro-methanolic extract prepared from the leaf, stem bark and flower of Bauhinia variegata were assessed for their antitumor activity. The extracts at doses of 500 and 750 mg/kg b.wt. were given orally along with cyclophosphamide (chemotherapeutic drug) for 40 days for exploring antitumor activity against melanoma tumor (B16F10) in C57BL mice. Inhibition of tumor growth, increase in survival time of animal with treatment, histopathological studies and antioxidant parameter were determined. Results: The Present investigation showed significant effect of the B. variegata L. in preventing melanoma tumor by B16F10 cell line in C57BL/6 mice. As compared with the tumour control group, the remarkable results especially in the group which received B. variegata extract and cyclophosphamide together were obtained for all of the measured parameters. Dose dependent response was observed in tumor volume, inhibition rate, life span time and antioxidant parameter of extracts. Combination treatment of cyclophosphamide and B. variegata extracts showed more pronounced effect. Conclusions: These findings suggest that B. variegata hydromethanolic extract may contain bioactive compounds of potential therapeutic significance which are relatively safe from toxic effects, and can compromise the medicinal use of this plant in folk medicine.

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Upregulation of phase II enzymes through phytochemical activation of Nrf2 protects cardiomyocytes against oxidant stress

Cited by 90 publications

References 50 publications

Activating Transcription Factor 3 Protects against Pressure-Overload Heart Failure via the Autophagy Molecule Beclin-1 Pathway

Activating Transcription Factor 3 Protects against Pressure-Overload Heart Failure via the Autophagy Molecule Beclin-1 Pathway

Effects of naringenin and its phase II metabolites onin vitrohuman macrophage gene expression

In vivo antitumor potential of extracts from different parts of Bauhinia variegata linn. Against b16f10 melanoma tumour model in c57bl/6 mice

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