Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases

Nature Reviews Drug Discovery, Journal Year: 2019, Volume and Issue: 18(4), P. 295 - 317

Published: Jan. 4, 2019

Language: Английский

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Nrf2 at the heart of oxidative stress and cardiac protection

Physiological Genomics, Journal Year: 2017, Volume and Issue: 50(2), P. 77 - 97

Published: Nov. 29, 2017

The NFE2L2 gene encodes the transcription factor Nrf2 best known for regulating expression of antioxidant and detoxification genes. Gene knockout approaches have demonstrated its universal cytoprotective features. While has been topic intensive research in cancer biology since discovery 1994, understanding role cardiovascular disease just begun. literature concerning experimental models atherosclerosis, ischemia, reperfusion, cardiac hypertrophy, heart failure, diabetes supports protective character. In addition to genes, found regulate genes participating cell signaling, transcription, anabolic metabolism, autophagy, proliferation, extracellular matrix remodeling, organ development, suggesting that governs damage resistance as well wound repair tissue remodeling. A long list small molecules, most derived from natural products, characterized inducers. These compounds disrupt Keap1-mediated ubquitination, thereby prohibiting proteasomal degradation allowing protein accumulate translocate nucleus, where interacts with sMaf bind ARE promoter Recently alternative mechanisms driving increase revealed, including removal Keap1 by autophagy due p62/SQSTM1 binding, inhibition βTrCP or Synoviolin/Hrd1-mediated ubiquitination Nrf2, de novo translation. We review here a large volume reporting historical recent discoveries about function regulation gene. Multiple lines evidence presented support potential dialing up pathway protection clinic.

Language: Английский

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The role of itaconate in host defense and inflammation

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(2)

Published: Jan. 17, 2022

Macrophages exposed to inflammatory stimuli including LPS undergo metabolic reprogramming facilitate macrophage effector function. This supports phagocytic function, cytokine release, and ROS production that are critical protective responses. The Krebs cycle is a central pathway within all mammalian cell types. In activated macrophages, distinct breaks in the regulate function through accumulation of several metabolites were recently shown have signaling roles immunity. One metabolite accumulates macrophages because disturbance itaconate, which derived from cis-aconitate by enzyme decarboxylase (ACOD1), encoded immunoresponsive gene 1 (Irg1). Review focuses on itaconate’s emergence as key immunometabolite with diverse immunity inflammation. These include inhibition succinate dehydrogenase (which controls levels succinate, multiple inflammation), glycolysis at will limit activation antiinflammatory transcription factors Nrf2 ATF3, NLRP3 inflammasome. Itaconate its derivatives effects preclinical models sepsis, viral infections, psoriasis, gout, ischemia/reperfusion injury, pulmonary fibrosis, pointing possible itaconate-based therapeutics for range diseases. intriguing continues yield fascinating insights into role host defense

Language: Английский

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The Nrf2/HO‐1 Axis in Cancer Cell Growth and Chemoresistance

Oxidative Medicine and Cellular Longevity, Journal Year: 2015, Volume and Issue: 2016(1)

Published: Nov. 30, 2015

The transcription factor, nuclear factor erythroid 2 p45‐related (Nrf2), acts as a sensor of oxidative or electrophilic stresses and plays pivotal role in redox homeostasis. Oxidative agents cause conformational change the Nrf2 inhibitory protein Keap1 inducing translocation which, through its binding to antioxidant/electrophilic response element (ARE/EpRE), regulates expression antioxidant detoxifying genes such heme oxygenase 1 (HO‐1). HO‐1 are frequently upregulated different types tumours correlate with tumour progression, aggressiveness, resistance therapy, poor prognosis. This review focuses on Nrf2/HO‐1 stress mechanism promising target for anticancer treatment which is able overcome therapies.

Language: Английский

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Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection

Pharmacological Research, Journal Year: 2015, Volume and Issue: 97, P. 84 - 103

Published: May 3, 2015

Language: Английский

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Interplay between food and gut microbiota in health and disease

Food Research International, Journal Year: 2018, Volume and Issue: 115, P. 23 - 31

Published: July 30, 2018

Language: Английский

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Inhibition of cancer antioxidant defense by natural compounds

Oncotarget, Journal Year: 2016, Volume and Issue: 8(9), P. 15996 - 16016

Published: Nov. 30, 2016

// Alicja Sznarkowska 1 , Anna Kostecka Katarzyna Meller and Krzysztof Piotr Bielawski Department of Biotechnology, Intercollegiate Faculty University Gdansk Medical Gdansk, Poland Correspondence to: Sznarkowska, email: Keywords : antioxidants, ROS, cancer, natural compounds, polyphenols Received September 02, 2016 Accepted November 22, Published 30, Abstract All classic, non-surgical anticancer approaches like chemotherapy, radiotherapy or photodynamic therapy kill cancer cells by inducing severe oxidative stress. Even tough chemo- are still a gold standard in treatment, the identification non-toxic compounds that enhance their selectivity, would allow for lowering doses, reduce side effects risk second cancers. Many products have ability to sensitize stress induced limiting antioxidant capacity cells. Blocking defense tumors decreases balance insult results cell death. Though one should bear mind same compound often exerts both anti-oxidant pro-oxidant properties, depending on concentration used, type, exposure time environmental conditions. Here we present comprehensive overview inhibit major mechanisms discuss potential clinical application.

Language: Английский

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The chemistry of gut microbial metabolism of polyphenols

Phytochemistry Reviews, Journal Year: 2016, Volume and Issue: 15(3), P. 425 - 444

Published: March 11, 2016

Language: Английский

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Hesperetin relieves cisplatin-induced acute kidney injury by mitigating oxidative stress, inflammation and apoptosis

Chemico-Biological Interactions, Journal Year: 2019, Volume and Issue: 308, P. 269 - 278

Published: May 31, 2019

Language: Английский

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Revisiting the Oxidation of Flavonoids: Loss, Conservation or Enhancement of Their Antioxidant Properties

Antioxidants, Journal Year: 2022, Volume and Issue: 11(1), P. 133 - 133

Published: Jan. 7, 2022

Flavonoids display a broad range of health-promoting bioactivities. Among these, their capacity to act as antioxidants has remained most prominent. The canonical reactive oxygen species (ROS)-scavenging mode the antioxidant action flavonoids relies on high susceptibility phenolic moieties undergo oxidation. As consequence, upon reaction with ROS, is severely compromised. Other phenol-compromising reactions, such those involved in biotransformation flavonoids, can also markedly affect properties. In recent years, however, increasing evidence indicated that, at least for some oxidation residues fact enhance original apparent paradoxical cases, activity arises from pro-oxidant and/or electrophilic character oxidation-derived metabolites and exerted by activating Nrf2-Keap1 pathway, which upregulates cell's endogenous capacity, and/or, preventing activation pro-inflammatory NF-κB pathway. This review focuses effects that oxidative non-oxidative modification groups may have ability resulting promote direct indirect actions. Considering case metabolite quercetin, we offer comprehensive description increasingly supports concept certain phenolics emerges mechanism amplifies An overlooked topic great phytomedicine potential thus unraveled.

Language: Английский

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