Superoxide dismutase 3 is induced by antioxidants, inhibits oxidative DNA damage and is associated with inhibition of estrogen-induced breast cancer

Singh, Bhupendra; Bhat, Hari K.

doi:10.1093/carcin/bgs300

Cited by 88 publications

(86 citation statements)

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“…Moreover, increasing Nrf2 level leads to the upregulation of MnSOD and EcSOD. [30][31][32][33][34] In this study, Nrf2 expression was induced by miR-424, suggesting that it is a target of miR-424 regulation; in addition, the protective function of miR-424 on neuron was inhibited by Nrf2 depletion and SOD inhibition. These results demonstrate that miR-424 positively regulates the endogenous antioxidant system in neurons, providing protection against oxidative damage during transient cerebral I/R.…”

mentioning

confidence: 51%

“…Экспрессия Mn-СОД в ответ на оксидантный стресс отличается в зависимости от используемой модели; однако микроРНК-424 может активировать экспрессию СОД независимо от условий эксперимента. Кроме того, повышение уровня Nrf2 при-водит к усилению активности Mn-СОД и Ec-СОД [30][31][32][33][34]. В этом исследовании, экспрессия Nrf2 была инду-цирована введением микроРНК-424, позволяя предпо-ложить, что Nrf2 является целью для микроРНК-424; кроме того, защитная функция микроРНК-424 в отно-шении нейронов подавлялась снижением Nrf2 и инги-битором СОД.…”

Section: рисунок 4 микрорнк-424 стимулируют экспрессию и активность unclassified

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MicroRNA-424 Protects Against Focal Cerebral Ischemia and Reperfusion Injury in Mice by Suppressing Oxidative Stress

Liu

Zhao

Wang

et al. 2015

Stroke

165

102

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513I schemic stroke is one of the leading causes of death and disability in the world, resulting from the disruption of blood supply to the brain. Intervention requires the restoration of blood flow, which can lead to reperfusion injury. Oxidative stress is thought to be the primary event during this process 1 because reperfusion stimulates an overproduction of reactive oxygen species (ROS), such as hydrogen peroxide (H 2 O 2 ), which leads to the oxidation of proteins, lipids, and DNA and can induce cell proliferation, growth arrest, apoptosis, and necrosis.2 Meanwhile, the dysfunction of superoxide dismutase (SOD) and glutathione peroxidase can compromise endogenous antioxidant defense mechanisms and further exacerbate oxidative stress and ischemic/reperfusion (I/R) injury.3,4 Nuclear factor erythroid 2-related factor (Nrf)2 activates the transcription of antioxidant stress genes whose products act concertedly to remove ROS through sequential enzymatic reactions. 5 Studies have uncovered the potential for Nrf2-mediated transcription to protect from neurodegeneration resulting from mechanisms involving oxidative stress. For this reason, Nrf2 is considered a valuable therapeutic target for free radical damage in brain after ischemia and reperfusion.MicroRNAs (miRs) are small (≈22 nt), noncoding, singlestranded RNA molecules that regulate gene expression at the posttranscriptional level by inhibiting translation or by cleaving RNA transcripts in a sequence-specific manner.6 MiR-424 is a tumor marker that is involved in cancer cell proliferation, Background and Purpose-We previously showed that the microRNA miR-424 protects against permanent cerebral ischemic injury in mice by suppressing microglia activation. This study investigated the role of miR-424 in transient cerebral ischemia in mice with a focus on oxidative stress-induced neuronal injury. Methods-Transient cerebral ischemia was induced in C57/BL6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion (ischemia/reperfusion). The miR-424 level in the peri-infarct cortex was quantified. Mice were also administered miR-424 angomir by intracerebroventricular injection. Cerebral infarct volume, neuronal apoptosis, and levels of oxidative stress markers and antioxidants were evaluated. In an in vitro experiment, primary cortical neurons were exposed to H 2 O 2 and treated with miR-424 angomir, nuclear factor erythroid 2-related factor 2 siRNA, and superoxide dismutase (SOD) inhibitor; cell activity, lactate dehydrogenase release, malondialdehyde level, and manganese (Mn)SOD activity were then evaluated. Results-MiR-424 levels in the peri-infarct cortex increased at 1 and 4 hours then decreased 24 hours after reperfusion.Treatment with miR-424 decreased infarct volume and inhibited neuronal apoptosis after ischemia/reperfusion, reduced reactive oxygen species and malondialdehyde levels in the cortex, and increased the expression and activation of MnSOD as well as the expression of extracellular SOD and the redox-sensitive transcription fact...

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confidence: 51%

Section: рисунок 4 микрорнк-424 стимулируют экспрессию и активность unclassified

MicroRNA-424 Protects Against Focal Cerebral Ischemia and Reperfusion Injury in Mice by Suppressing Oxidative Stress

Liu

Zhao

Wang

et al. 2015

Stroke

165

102

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“…These results as well as the results of the present study indicate that NRF2 plays an important role in the increased proliferative activity of breast carcinoma cells. On the other hand, previous reports had also indicated the protective role of NRF2 against DNA damage and mammary carcinogenesis in non-neoplastic breast epithelial cells (Singh & Bhat 2012, Singh et al 2013, and Becks et al (2010) reported that Nrf2-knockout mice were more susceptible to mammary carcinogenesis. Therefore, NRF2 may have dual roles in breast carcinoma, i.e.…”

Section: Discussionmentioning

confidence: 96%

NRF2 immunolocalization in human breast cancer patients as a prognostic factor

Onodera¹,

Motohashi²,

Takagi³

et al. 2013

Endocrine-Related Cancer

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Nuclear factor erythroid 2-related factor 2 (NRF2 (NFE2L2)) is an important transcriptional activator involved in the cellular defense mechanisms against electrophilic and oxidative stress. Recent studies have demonstrated that the expression of NRF2 protein is upregulated in several human malignancies and is associated with worse prognosis in these patients. However, the pathological and clinical significance of NRF2 has remained largely unknown in breast cancer patients. Therefore, in this study, we immunolocalized NRF2 in 106 breast carcinoma cases. NRF2 immunoreactivity was mainly detected in the nucleus of the breast carcinoma cells and it was positive in 44% of the cases. NRF2 status was significantly associated with histological grade, Ki-67 labeling index, p62 immunoreactivity, and NAD(P) H:quinone oxidoreductase 1 (NQO1) immunoreactivity, and the results of multivariate analyses revealed that NRF2 status was an independent adverse prognostic factor for both recurrence and disease-free survival of the patients. Subsequent in vitro studies demonstrated that the expression of NRF2 significantly increased the proliferation activity of MCF7 and SK-BR-3 breast carcinoma cells. These results indicate that nuclear NRF2 protein plays important roles in the proliferation and/or progression of breast carcinoma, and nuclear NRF2 immunoreactivity is therefore considered a potent prognostic factor in breast cancer patients.

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“…Forty microgram total protein, isolated from quadruplicates of control or treated cells, was size fractionated on a 12% SDS-polyacrylamide gel, and transferred onto PVDF membranes under standard conditions [5, 13, 43–45]. Membranes were blocked in 5% dry non-fat milk/PBS/0.05% Tween-20 at four degrees in a refrigerator overnight.…”

Section: Methodsmentioning

confidence: 99%

Differential regulation of estrogen receptors α and β by 4-(E)-{(4-hydroxyphenylimino)-methylbenzene,1,2-diol}, a novel resveratrol analog

Ronghe

Chatterjee

Singh

et al. 2014

The Journal of Steroid Biochemistry and Molecular Biology

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Breast cancer is the second leading cause of death among women in the United States. Estrogens have been implicated as major risk factors in the development of breast neoplasms. Recent epidemiologic studies have suggested a protective role of phytoestrogens in prevention of breast and other cancers. Resveratrol, a naturally occurring phytoestrogen found notably in red grapes, berries and peanuts, has been shown to possess potent anti-cancer properties. However, the poor efficacy of resveratrol has prevented its use in a clinical setting. In order to improve the efficacy of resveratrol, we have synthesized a small combinatorial library of azaresveratrol analogs and tested them for their ability to inhibit the growth of breast cancer cell lines. We have recently shown that one of the synthesized analogs, 4-(E)-{(4-hydroxyphenylimino)-methylbenzene, 1, 2-diol} (HPIMBD), has better anti-cancer properties than resveratrol. The objective of this study was to investigate the differential regulation of estrogen receptors (ERs) α and β as a potential mechanism of inhibition of breast cancer by HPIMBD. Estrogen receptors α and β have been shown to have opposing roles in cellular proliferation. Estrogen receptor α mediates the proliferative responses of estrogens while ERβ plays an anti-proliferative and pro-apoptotic role. We demonstrate that HPIMBD significantly induces the expression of ERβ and inhibits the expression of ERα. HPIMBD also inhibits the protein expression levels of oncogene c-Myc, and cell cycle protein cyclin D1, genes downstream to ERα and important regulators of cell cycle, and cellular proliferation. HPIMBD significantly induces protein expression levels of tumor suppressors p53 and p21 in MCF-7 cells. Additionally, HPIMBD inhibits c-Myc in an ERβ-dependent fashion in MCF-10A and ERβ1-transfected MDA-MB-231 cells, suggesting regulation of ERs as an important upstream mechanism of this novel compound. Molecular docking studies confirm higher affinity for binding of HPIMBD in the ERβ cavity. Thus, HPIMBD, a novel azaresveratrol analog may inhibit the proliferation of breast cancer cells by differentially modulating the expressions of ERs α and β.

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Superoxide dismutase 3 is induced by antioxidants, inhibits oxidative DNA damage and is associated with inhibition of estrogen-induced breast cancer

Cited by 88 publications

References 51 publications

MicroRNA-424 Protects Against Focal Cerebral Ischemia and Reperfusion Injury in Mice by Suppressing Oxidative Stress

MicroRNA-424 Protects Against Focal Cerebral Ischemia and Reperfusion Injury in Mice by Suppressing Oxidative Stress

NRF2 immunolocalization in human breast cancer patients as a prognostic factor

Differential regulation of estrogen receptors α and β by 4-(E)-{(4-hydroxyphenylimino)-methylbenzene,1,2-diol}, a novel resveratrol analog

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