Involvement of Nrf2 in myocardial ischemia and reperfusion injury

International Journal of Biological Macromolecules, Journal Year: 2018, Volume and Issue: 125, P. 496 - 502

Published: Nov. 20, 2018

Language: Английский

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Epigenetic regulation of Keap1-Nrf2 signaling

Free Radical Biology and Medicine, Journal Year: 2015, Volume and Issue: 88, P. 337 - 349

Published: June 24, 2015

Language: Английский

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AMPK and NRF2: Interactive players in the same team for cellular homeostasis?

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 190, P. 75 - 93

Published: July 31, 2022

NRF2 (Nuclear factor E2 p45‐related 2) is a stress responsive transcription lending cells resilience against oxidative, xenobiotic, and also nutrient or proteotoxic insults. AMPK (AMP-activated kinase), considered as prime regulator of cellular energy homeostasis, not only tunes metabolism to provide the cell at any time with sufficient ATP building blocks, but controls redox balance inflammation. Due observed overlapping responses upon activation common stressors impinging on both signaling, it plausible assume that signaling may interdepend cooperate readjust homeostasis. After short introduction two players this narrative review paints current picture how might interact molecular level, highlights their possible crosstalk in selected examples pathophysiology bioactivity drugs phytochemicals.

Language: Английский

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Epigenetic regulation in cancer therapy: From mechanisms to clinical advances

MedComm – Oncology, Journal Year: 2024, Volume and Issue: 3(1)

Published: Jan. 4, 2024

Abstract Epigenetic regulation refers to the alteration of gene expression independent changes in DNA sequence. It involves chemical modifications such as methylation, histone and acetylation, which are regulated by a coordinated interplay various regulators ensure precise spatial temporal expression. aberrations commonly observed cancer considered hallmarks cancer. In recent years, small molecules targeting specific epigenetic have been developed demonstrating promising therapeutic potential preclinical clinical trials for treatment. this review, we summarize essential regulatory mechanisms dysfunctions involved acetylation during tumor development progression. Moreover, discuss current advances challenges therapy that target these both hematologic malignancies solid tumors. Finally, combining drugs with other therapies, including chemotherapy, radiotherapy, targeted therapy, immunotherapy, approach Overall, aim enhance understanding explore strategies based on mechanisms, ultimately advance improve patient prognosis.

Language: Английский

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ZMYND8 protects breast cancer stem cells against oxidative stress and ferroptosis through activation of NRF2

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(6)

Published: Jan. 23, 2024

Breast cancer stem cells (BCSCs) mitigate oxidative stress to maintain their viability and plasticity. However, the regulatory mechanism of in BCSCs remains unclear. We recently found that histone reader ZMYND8 was upregulated BCSCs. Here, we showed reduced ROS iron inhibit ferroptosis aldehyde dehydrogenase–high (ALDHhi) BCSCs, leading BCSC expansion tumor initiation mice. The underlying involved a two-fold posttranslational regulation nuclear factor erythroid 2–related 2 (NRF2). increased stability NRF2 protein through KEAP1 silencing. On other hand, interacted with recruited promoters antioxidant genes enhance gene transcription mammospheres. phenocopied stemness by inhibiting ferroptosis. Loss counteracted ZMYND8's effects on Interestingly, expression directly controlled Collectively, these findings uncover positive feedback loop amplifies defense sustaining survival stemness.

Language: Английский

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Multiple regulations of Keap1/Nrf2 system by dietary phytochemicals

Molecular Nutrition & Food Research, Journal Year: 2016, Volume and Issue: 60(8), P. 1731 - 1755

Published: April 11, 2016

Keap1/Nrf2 system plays a critical role on cellular protection by regulating many antioxidant and detoxification enzyme genes through the response element (ARE). Thus, it must work constantly to prevent accumulation of reactive oxygen species (ROS) because excess ROS are associated with diseases such as cancer, cardiovascular complications, inflammation, neurodegeneration. Dietary phytochemicals widely distributing in fruits vegetables have been considered possess cancer chemopreventive potential induction system‐mediated enzymes variety manners. The data extensive not well classified molecular mechanisms. In this review, we first briefly introduce current knowledge regulation including Keap1‐dependent Keap1‐independent cascades, epigenetic pathway. Then, summarize targets dietary phytochemicals, finally review crosstalk between other signaling pathways regulate diverse chronic phytochemicals. These comprehensive will help us understand effects prevention maintenance human health.

Language: Английский

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SIRT5 facilitates cancer cell growth and drug resistance in non-small cell lung cancer

Tumor Biology, Journal Year: 2014, Volume and Issue: 35(11), P. 10699 - 10705

Published: July 28, 2014

Lung cancer is one of the leading causes cancer-related death in developed countries. Despite decades intensive efforts to comate this malignant disease, prognosis lung remains unfavorable and especially poor advanced non-small cell (NSCLC). Accumulating evidence indicate that main outcome NSCLC treatment innate resistance patients anticancer drugs. However, mechanism underling development drug not fully understood. Here we show mitochondrial class III NAD+-dependent deacetylase SIRT5 overexpressed human high expression predicts survival. knockdown represses growth transformation vitro vivo. Furthermore, find makes cells more sensitive (cis-diamminedichloroplatinum [CDDP], 5-fluorouracil [5-FU] or bleomycin) Mechanically, identify Nrf2, which a core transcription factor for resistance, as target SIRT5. mRNA level positively correlated with Nrf2 tissues reduces its downstream drug-resistance genes. Taken together, our findings implicate protein responsible NSCLC, may serve potential prognostic intervention.

Language: Английский

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MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria

Cell, Journal Year: 2016, Volume and Issue: 167(3), P. 722 - 738.e23

Published: Oct. 1, 2016

Language: Английский

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Mitochondrial Sirtuins and Their Relationships with Metabolic Disease and Cancer

Antioxidants and Redox Signaling, Journal Year: 2014, Volume and Issue: 22(12), P. 1060 - 1077

Published: Dec. 29, 2014

Maintenance of metabolic homeostasis is critical for cellular and organismal health. Proper regulation mitochondrial functions represents a crucial element overall homeostasis. Mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) play pivotal roles in promoting this by regulating numerous aspects metabolism response to environmental stressors.New work has illuminated multiple links between cancer. SIRT5 been shown regulate the recently described post-translational modifications succinyl-lysine, malonyl-lysine, glutaryl-lysine. An understanding these still its infancy. Enumeration SIRT3 targets via advanced proteomic techniques promises dramatically enhance insight into proteins.In review, we highlight their Furthermore, discuss emerging suppressing and/or tumorigenesis, depending on molecular context.Currently, hundreds potential have identified experiments. Future studies will need validate major enzymes, elucidate how acetylation acylation modulate functionality. A great deal interest exists targeting pharmacologically; endeavor require development sirtuin-specific modulators (activators inhibitors) as treatments cancer disease.

Language: Английский

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Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters

Drug Metabolism Reviews, Journal Year: 2016, Volume and Issue: 48(4), P. 541 - 567

Published: June 20, 2016

Chemoresistance is a disturbing barrier in cancer therapy, which always results limited therapeutic options and unfavorable prognosis. Nuclear factor E2-related 2 (NRF2) controls the expression of genes encoding cytoprotective enzymes transporters that protect against oxidative stress electrophilic injury to maintain intrinsic redox homeostasis. However, recent studies have demonstrated aberrant activation NRF2 due genetic and/or epigenetic mutations tumor contributes high phase I II drug-metabolizing enzymes, III transporters, other proteins, leads decreased efficacy anticancer drugs through biotransformation or extrusion during chemotherapy. Therefore, better understanding role regulation these tumors necessary find new strategies improve chemotherapeutic efficacy. In this review, we summarized findings about chemoresistance-promoting NRF2, NRF2-regulated drug efflux genes. Most importantly, potential was proposed counteract resistance treatment.

Language: Английский

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