Epigenetic regulation of Keap1-Nrf2 signaling

Guo, Yue; Yu, Siwang; Zhang, Chengyue; Kong, Ah Ng Tony

doi:10.1016/j.freeradbiomed.2015.06.013

Cited by 204 publications

(153 citation statements)

References 122 publications

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“…We hypothesized that 1 mechanism might be the KEAP-1/nuclear factor erythroid-derived-2-related-factor (Nrf2)/antioxidant pathway, widely recognized as a prominent regulator of antioxidant enzyme gene expression (32)(33)(34)(35)(36). Several reports involving mouse models of diabetes appeared midway through our study and supported this possibility (6,(37)(38)(39).…”

Section: Introductionsupporting

confidence: 51%

Nrf2/antioxidant pathway mediates β cell self-repair after damage by high-fat diet–induced oxidative stress

Abebe¹,

Mahadevan²,

Bogachus³

et al. 2017

JCI Insight

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Section: Introductionsupporting

confidence: 51%

Nrf2/antioxidant pathway mediates β cell self-repair after damage by high-fat diet–induced oxidative stress

Abebe¹,

Mahadevan²,

Bogachus³

et al. 2017

JCI Insight

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“…As numerous pathways are converging at Nrf2, many details still remain to be clarified. An aspect of particular relevance to aging as well as to chronic age-related diseases concerns Nrf2-mediated protection against oxidative stress, which is typically associated with senescence [15,88]. These findings are well in accordance with similar effects observed with melatonin [52,[90][91][92][93].…”

Section: Chromatin Remodeling By Circadian Oscillators and Melatoninsupporting

confidence: 76%

“…The role of Nrf2 is of utmost interest to epigenetics. On the one hand, epigenetic mechanisms at various levels (DNA methylation/ demethylation, histone acetylation/deacetylation, histone methylation/demethylation, microRNAs) are involved in the regulation of Nrf2 and its negative regulator kelch-like ECH-associated protein 1 (Keap1), whereas, on the other hand, Nrf2 likely exerts epigenetic effects, e.g., by promoting site-specific histone acetylation and/or inhibition of histone deacetylation [88,89]. As numerous pathways are converging at Nrf2, many details still remain to be clarified.…”

Section: Chromatin Remodeling By Circadian Oscillators and Melatoninmentioning

confidence: 99%

Untitled

2017

J Geriatr Med Gerontol

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Melatonin is a highly pleiotropic regulator molecule that influences numerous functions in many cell types. Its actions comprise direct and circadian oscillator-mediated effects. The levels of circulating melatonin typically decline in the course of aging. Additionally,various aging-associated diseases further decrease melatonin concentrations. With regard to its remarkably broad spectrum of actions, control mechanisms upstream and downstream of melatonin should be investigated much more in detail with regard to the contribution of epigenetic modulation. The importance of epigenetic alterations has already become evident in the fields of both gerontology and chronobiology. Therefore, it seems necessary to fill the gaps concerning corresponding processes related to melatonin, especially under the aspects of physiologic malfunctions because of aging-associated decreases of melatonin. This review outlines the findings on melatonin's epigenetic actions, as obtained to date, and sets these results in correspondence to general knowledge and many specific findings concerning circadian rhythms. These considerations focus on DNA methylation and erasure of 5-methylcytosine, on histone modification, in particular, acetylation/deacetylation and methylation/demethylation, and on the manifold roles of noncoding RNAs, especially microRNAs. With regard to melatonin's spectrum of actions in the gerontological context, emphasis is given to its contribution to circadian oscillation amplitudes, to anti-inflammatory actions and to antioxidative protection.

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“…It has been reported that several miRNAs, such as miR‐144, miR‐28, and miR‐153, can negatively regulate Nrf2 levels by directly targeting the 3'UTR of Nrf2 mRNA 36, 37. Here, miR‐365 was identified as a novel miRNA that decreases Nrf2 levels by binding to its 3'UTR.…”

Section: Discussionmentioning

confidence: 97%

LncRNA MT1DP Aggravates Cadmium‐Induced Oxidative Stress by Repressing the Function of Nrf2 and is Dependent on Interaction with miR‐365

Gao

et al. 2018

Advanced Science

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Although cadmium (Cd)‐induced hepatoxicity is well established, pronounced knowledge gaps remain existed regarding the inherent cellular signaling that dictates Cd toxicity. Specifically, the molecular basis for determining the equilibrium between prosurvival and proapoptotic signaling remains poorly understood. Thus, it is recently revealed that long non‐coding RNA (lncRNA) MT1DP, a pseudogene in the metallothionein (MT) family, promoted Cd‐induced cell death through activating the RhoC‐CCN1/2‐AKT pathway and modulating MT1H induction. Here, first the dependency of MT1DP induction on MTF1, an important transcriptional factor in driving the mRNA expression of MT1 members is defined. Additionally, a bridge molecule between MT1DP and nuclear factor erythroid 2‐related factor 2 (Nrf2) is established: miR‐365. Mechanistically, MT1DP induction under Cd stress decreases the nuclear factor erythroid 2‐related factor 2 (Nrf2) level to evoke oxidative stress through the elevation of miR‐365, which acted to repress the Nrf2 level via direct binding to its 3'UTR. In contrast to the competing endogenous RNA (ceRNA) mechanism, a new mechanism is proposed: MT1DP elevated the miR‐365 level though stabilizing its RNA via direct binding. Collectively, the combined data demonstrate a crucial role of MT1DP in reducing the Nrf2‐mediated protection of cells, and this is dependent on the interplay with miR‐365. Hence, the study further expands the knowledge of inducible endogenous lncRNA in modulating oxidative stress.

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Epigenetic regulation of Keap1-Nrf2 signaling

Cited by 204 publications

References 122 publications

Nrf2/antioxidant pathway mediates β cell self-repair after damage by high-fat diet–induced oxidative stress

Nrf2/antioxidant pathway mediates β cell self-repair after damage by high-fat diet–induced oxidative stress

Untitled

LncRNA MT1DP Aggravates Cadmium‐Induced Oxidative Stress by Repressing the Function of Nrf2 and is Dependent on Interaction with miR‐365

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