Natural Product Reports, Journal Year: 2020, Volume and Issue: 37(6), P. 797 - 826
Published: Jan. 1, 2020
NRF2 is a transcription factor that activated by many natural products for chemoprevention, but aberrant activation can lead to disease and have been used inhibit the pathway.
Language: Английский
Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 21(7), P. 363 - 383
Published: March 30, 2020
Language: Английский
Citations
3514
Antioxidants, Journal Year: 2019, Volume and Issue: 8(7), P. 235 - 235
Published: July 22, 2019
Poultry in commercial settings are exposed to a range of stressors. A growing body information clearly indicates that excess ROS/RNS production and oxidative stress major detrimental consequences the most common stressors poultry production. During evolution, antioxidant defence systems were developed survive an oxygenated atmosphere. They include complex network internally synthesised (e.g., enzymes, (glutathione) GSH, (coenzyme Q) CoQ) externally supplied (vitamin E, carotenoids, etc.) antioxidants. In fact, all antioxidants work cooperatively as team maintain optimal redox balance cell/body. This is key element providing necessary conditions for cell signalling, vital process regulation expression various genes, adaptation homeostasis maintenance body. Since considered be important signalling molecules, their concentration strictly regulated by conjunction with transcription factors vitagenes. activation vitagenes via such Nrf2 leads additional synthesis array protective molecules which can deal increased Therefore, it challenging task develop system supplementation help growing/productive birds effective defences On one hand, antioxidants, vitamin or minerals Se, Mn, Cu Zn) compulsory part pre-mixes poultry, and, cases, adequate meet physiological requirements these elements. other due aforementioned commercially relevant stressors, there need support poultry. new direction improving related opportunity activate (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH thioredoxin, Heat shock protein (HSP)/heat factor (HSP), sirtuins, maximise internal AO protection maintenance. development vitagene-regulating nutritional supplements on agenda many companies worldwide.
Language: Английский
Citations
469
Antioxidants, Journal Year: 2022, Volume and Issue: 11(12), P. 2345 - 2345
Published: Nov. 27, 2022
Organisms are continually exposed to exogenous and endogenous sources of reactive oxygen species (ROS) other oxidants that have both beneficial deleterious effects on the cell. ROS important roles in a wide range physiological processes; however, high levels associated with oxidative stress disease progression. Oxidative has been implicated nearly all major human diseases, from neurogenerative diseases neuropsychiatric disorders cardiovascular disease, diabetes, cancer. Antioxidant defence systems evolved as means protection against stress, transcription factor Nrf2 key regulator. is responsible for regulating an extensive panel antioxidant enzymes involved detoxification elimination extensively studied contexts. This review aims provide reader general overview Nrf2, including basic mechanisms activation regulation, implications various diseases.
Language: Английский
Citations
363
Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)
Published: Jan. 1, 2021
Oxidative stress, a term that describes the imbalance between oxidants and antioxidants, leads to disruption of redox signals causes molecular damage. Increased oxidative stress from diverse sources has been implicated in most senescence‐related diseases aging itself. The Kelch‐like ECH‐associated protein 1‐ (Keap1‐) nuclear factor‐erythroid 2‐related factor 2 (Nrf2) system can be used monitor stress; Keap1‐Nrf2 is closely associated with controls transcription multiple antioxidant enzymes. Simultaneously, signaling also modulated by more complex regulatory network, including phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt), C, mitogen‐activated kinase. This review presents information on aging‐related mechanisms involving Keap1‐Nrf2. Furthermore, we highlight several major involved Nrf2 unbinding Keap1, cysteine modification Keap1 phosphorylation Nrf2, PI3K/Akt/glycogen synthase 3 β , sequestosome 1, Bach1 c ‐ Myc . Additionally, discuss direct interaction mammalian target rapamycin pathway. In summary, focus recent progress research aging, providing an empirical basis for development antiaging drugs.
Language: Английский
Citations
314
Cell chemical biology, Journal Year: 2020, Volume and Issue: 27(4), P. 436 - 447
Published: April 1, 2020
Ferroptosis is a non-apoptotic mode of regulated cell death that iron and lipid peroxidation dependent. As new mechanistic insight into ferroptotic effectors how they are in different disease contexts uncovered, our understanding the physiological pathological relevance this continues to grow. Along these lines, host pharmacological modulators pathway have been identified, targeting proteins involved homeostasis; generation reduction peroxides; or cystine import glutathione metabolism. Also, note, many components ferroptosis cascade target genes transcription factor nuclear erythroid 2-related 2 (NRF2), indicating its critical role mediating response. In review, we discuss vitro, vivo, clinical evidence disease, including brief discussion upstream mediators cascade, NRF2, treat ferroptosis-driven diseases.
Language: Английский
Citations
309
Trends in Pharmacological Sciences, Journal Year: 2020, Volume and Issue: 41(9), P. 598 - 610
Published: July 14, 2020
The host inflammatory response is a crucial determinant of disease outcome and correlates with severity in SARS-CoV-2-induced infection, for which there no treatment to date.Activation transcription factor nuclear erythroid 2 p45-related (NRF2) promotes resolution inflammation and, parallel, restores cellular redox protein homeostasis, facilitates tissue repair.NRF2 can be activated by pharmacological inducers that target Kelch-like ECH-associated 1 (KEAP1), the principal negative regulator NRF2.The available information on pharmacokinetics, pharmacodynamics, safety, efficacy NRF2 activators sulforaphane bardoxolone methyl (currently advanced clinical trials other indications) humans makes them excellent candidates testing randomized COVID-19. Acute respiratory distress syndrome (ARDS) caused SARS-CoV-2 largely result dysregulated response, followed damage alveolar cells lung fibrosis. Exacerbated proinflammatory cytokines release (cytokine storm) loss T lymphocytes (leukopenia) characterize most aggressive presentation. We propose multifaceted anti-inflammatory strategy based activation deployed against virus. provides robust cytoprotection restoring promoting inflammation, facilitating repair. such as are already trials. safety these modulators humans, together their well-documented cytoprotective effects preclinical models, highlight potential this armamentarium deployment battlefield Numerous observations during outbreaks coronaviruses – severe acute coronavirus (SARS-CoV), Middle East syndrome-related (MERS-CoV), recently convincingly show that, addition virus propagation, [1.Guan W.J. et al.Clinical characteristics 2019 China.N. Engl. J. Med. 2020; 382: 1861-1862Crossref PubMed Scopus (2383) Google Scholar]. A parallel drawn influenza, lethality not associated cytolytic action pathogen but instead orchestrated immune system [2.Galani I.E. Andreakos E. Neutrophils viral infections: current concepts caveats.J. Leukoc. Biol. 2015; 98: 557-564Crossref (47) In cases disease, cytokine storm (excess production cytokines) [3.Huang C. features patients infected novel Wuhan, China.Lancet. 395: 497-506Abstract Full Text PDF (4657) Scholar] cell depletion, pulmonary damage. Patients showing (ARDS; see Glossary) types virus-induced pneumonia also present macrophage (MAS) There evidence leukopenia, ~twofold decrease number [4.Qin al.Dysregulation COVID-19 China.Clin. Infect. Dis. (Published online March 12, 2020. https://doi.org/10.1093/cid/ciaa248)Crossref Scholar], may pyroptosis, form death mainly affects [5.Fung S.Y. al.A tug-of-war between antiviral defence: lessons from pathogenic viruses.Emerg. Microbes 9: 558-570Crossref (46) On hand, granulocytosis might partly responsible strong burst superoxide type reactive oxygen species (ROS) [6.Sies H. Jones D.P. Reactive pleiotropic physiological signalling agents.Nat. Rev. Mol. Cell 21: 363-383Crossref (20) additional [7.DeDiego M.L. al.Inhibition NF-kappaB-mediated coronavirus-infected mice increases survival.J. Virol. 2014; 88: 913-924Crossref (0) To comprehensively manage symptoms (the SARS-CoV-2), it understand appropriate context introducing an therapy complement therapy. Such must control without altering ability mount efficient adaptive boosting endogenous defenses targeting (gene name NFE2L2) will promote restore homeostasis facilitate It should noted under discussion distinctly separate identically abbreviated (also known GA binding subunit β, gene GABPB1), completely different involved mitochondrial biogenesis [8.Jornayvaz F.R. Shulman G.I. Regulation biogenesis.Essays Biochem. 2010; 47: 69-84Crossref cap'n'collar (CNC) heterodimerizes small musculoaponeurotic fibrosarcoma (sMAF) proteins, K, G, or F [9.Otsuki A. Yamamoto M. Cis-element architecture Nrf2–sMaf heterodimer sites its relation diseases.Arch. Pharm. Res. 43: 275-285Crossref factors C-JUN JUND [10.Venugopal R. Jaiswal A.K. Nrf2 Nrf1 association Jun proteins regulate antioxidant element-mediated expression coordinated induction genes encoding detoxifying enzymes.Oncogene. 1998; 17: 3145-3156Crossref bind elements (AREs), regulates genes, including those detoxification, macromolecular repair, metabolic balance [11.Cuadrado al.Therapeutic KEAP1 partnership chronic diseases.Nat. Drug Discov. 2019; 18: 295-317Crossref (134) Under basal conditions, interacts E3 ligase substrate adapter (KEAP1) targets ubiquitination proteasomal degradation Scholar, 12.Cuadrado al.Transcription therapeutic diseases: systems medicine approach.Pharmacol. 2018; 70: 348-383Crossref (110) 13.Hayes J.D. Dinkova-Kostova A.T. regulatory network interface intermediary metabolism.Trends Sci. 39: 199-218Abstract (759) (Figure 1, Key Figure). 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Longev. 2019: 7090534PubMed Moreover, single-nucleotide polymorphisms (SNPs) located promoter region NFE2L2 (encoding NRF2) implicated susceptibility hence reinforcing diseases [19.Acosta-Herrera al.Common variants predisposes sepsis.Crit. Care. 19: 256Crossref (9) Scholar,20.Hua C.C. al.Functional haplotypes obstructive disease.Dis. Markers. 28: 185-193Crossref plays role both execution [12.Cuadrado repressing IL6 IL1B [21.Kobayashi E.H. al.Nrf2 suppresses blocking transcription.Nat. 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May 27, http://dx.doi.org/10.21203/rs.3.rs-31855/v1)Google Interestingly, reciprocal crosstalk NF-κB inflamed tissues, innate recruited [34.Cuadrado NF-kappaB effectors Rho family, GTP-binding RAC1 inflammation.J. Chem. 289: 15244-15258Crossref (143) 35.Lastres-Becker I. al.Fractalkine NRF2/NFE2L2 heme oxygenase restrain tauopathy-induced microgliosis.Brain. 137: 78-91Crossref (63) 36.Boutten al.NRF2 targeting: promising disease.Trends 363-371Abstract (127) Following SARS-CoV, lungs monocyte vitro; inhibition decreases after SARS-CoV Scholar,37.Dosch S.F. al.SARS spike protein-induced occurs vitro.Virus 142: 19-27Crossref (33) Thus, limit NF-κB-mediated processes inflicted infection. genome encodes non-structural (nsp) replication, structural (S), envelope (E), membrane (M), nucleocapsid (N), accessory ORF3, 6, 7a, 7b, 8, 9b interact [38.Zhu N. China, 2019.N. 727-733Crossref (2517) receptor-binding domain (RBD) S angiotensin-converting enzyme (ACE2) allow entry 1) [39.Chen Y. al.Structure analysis 2019-nCoV.Biochem. Biophys. 525: 135-140Crossref (82) use ACE inhibitors/angiotensin-receptor blockers, widely prescribed cardiovascular pathologies [40.Lopes R.D. al.Continuing suspending inhibitors angiotensin blockers: impact adverse outcomes hospitalized (SARS-CoV-2) BRACE CORONA trial.Am. Heart 226: 49-59Crossref currently being considered (clinical trial numbersi NCT04311177 NCT04312009 losartan) because II, inhibitors, vasoconstrictive, proinflammatory, pro-oxidative, prothrombotic [41.Mehta P.K. Griendling K.K. Angiotensin II signaling: pathological system.Am. Physiol. 2007; 292: C82-C97Crossref (1226) However, alter ACE/ACE2 increase ACE2 levels, thus potentially increasing docking [42.Magrone T. al.Focus receptors special reference drug perspective.Endocr. Metab. Immune Disord. Targets. April https://doi.org/10.2174/1871530320666200427112902)Crossref (8) upregulate ACE2, whereas activator oltipraz reduces levels [43.Zhao upregulates intrarenal enzyme-2 1–7 attenuates hypertension nephropathy diabetic mice.Endocrinology. 159: 836-852Crossref suggesting reduce availability into 1). By analogy coronaviruses, expected modulate translational machinery generation own [44.Nakagawa K. al.Viral mRNA translation cells.Adv. Virus 96: 165-192Crossref (11) Host countermeasures step inactivation eukaryotic initiation (eIF2) two three eIF2α kinases, kinase R (PKR) PKR-like endoplasmic reticulum (PERK), [45.Krahling V. al.Severe triggers apoptosis resistant activity.J. 83: 2298-2309Crossref (35) PKR autophagy cargo p62, competes [46.Komatsu selective p62 responsive through Keap1.Nat. 12: 213-223Crossref (1145) further autophagic [47.Taguchi al.Keap1 maintenance homeostasis.Proc. 2012; 109: 13561-13566Crossref (237) transcriptional observed host-induced blockade protein, unfolded (UPR), PERK [48.Chan C.P. al.Modulation protein.J. 2006; 80: 9279-9287Crossref (71) phosphorylates [49.Cullinan S.B. direct effector PERK-dependent survival.Mol. 2003; 23: 7198-7209Crossref one at modulated cells. Cells recognize molecular patterns, especially nucleic acids, cytoplasmic endosomal receptors, retinoic acid-inducible I (RIG-I) melanoma differentiation-associated 5 (MDA-5) [50.Loo Y.M. al.Distinct RIG-I MDA5 immunity.J. 82: 335-345Crossref (692) cyclic GMP-AMP synthase (cGAS), signals adaptor stimulator interferon (STING) [51.Burdette D.L. al.STING di-GMP.Nature. 478: 515-518Crossref (677) detection activate 3 (IRF3)-mediated III interferons (IFNs) Coronavirus (including SARS-CoV) antagonize STING-mediated [52.Sun L. al.Coronavirus papain-like proteases negatively disruption signaling.PLoS One. 7e30802Crossref Scholar,53.Chen X. protease inhibits interaction STING–TRAF3–TBK1 complex.Protein 5: 369-381Crossref Although IFNs restricting spread autocrine paracrine IFN signaling, excessive resident exacerbate infiltration monocyte-derived macrophages, potentiating [54.Acharya D. responses COVID-19.Nat. Immunol. 20: 397-398Crossref downregulates production, part downregulating STING [55.Olagnier al.Activation augments vesicular stomatitis oncolysis autophagy-driven immunity.Mol. Ther. 25: 1900-1916Abstract (29) Scholar,56.Olagnier indicating link sensing reprogramming.Nat. 3506Crossref (31) Therefore, attenuate preventing IFNs. addition, upregulation NRF2-transcriptional (HO-1, HMOX1) linked many HIV, hepatitis C (HCV), B (HBV), enterovirus 71 (E71), virus, syncytial (RSV), Dengue (DENV), Ebola (EBOV) [57.Espinoza J.A. immunity oxygenase-1.Am. Pathol. 187: 487-493Abstract HO-1 forming heterodimeric complex IRF3 [58.Koliaraki Kollias G. new myeloid homeostasis.Adv. Exp. 780: 101-111Crossref With interaction, phosphorylated translocated nucleus 2). Several described HO-1, extrapolated some extent SARS-CoV-2. catalyzes products, biliverdin, Fe2+, CO, each putative anti-SARS-CoV-2 activity. Coronaviruses produce 3C-like proteinase (3CL-pro) (PLpro) process polyproteins essential [59.Bafna al.Structural similarity M(pro) HCV NS3/4A suggests approaches identifying existing drugs useful therapeutics.ChemRxiv. 21, http://dx.doi.org/10.26434/chemrxiv.12153615)PubMed Both 3CL-Pro PLpro share high homology [60.Baez-Santos SARS-coronavirus protease: structure, function designed compounds.Antivir. 115: 21-38Crossref inhibited biliverdin [61.Zhu Z. al.Biliverdin nonstructural 3/4A activity: mechanism oxygenase?.Hepatology. 52: 1897-1905Crossref (57) Biliverdin then 3CLpro PLpro. Free Fe2+ binds highly conserved divalent metal-binding pocket RdRp HCV, enzymatic 2) [62.Fillebeen al.Iron inactivates polymerase NS5B subgenomic Virus.J. 2005; 280: 9049-9057Crossref (80) Scholar,63.Fillebeen Pantopoulos Iron permissive Huh7.5.1 cells.J. Hepatol. 53: 995-999Abstract (44) Because [64.Gao RNA-dependent virus.Science. 368: 779-782Crossref similar NRF2/HO-1-mediated Furthermore, CO elicits positive-sense single-stranded (+ssRNA) E71 [65.Tung W.H. al.Enterovirus integrin beta1/EGFR-Rac1-dependent SK-N-SH cells: HO-1/CO replication.J. 3316-3329Crossref bovine diarrhea (BVDV9) [66.Ma al.Carbon monoxide suppress diarrhoea Gen. 2982-2992Crossref (2) effect phenocopied donor, CO-releasing molecule (CORM-2), depends soluble guanylyl cyclase (sGC), local cGMP G (PKG) turn, PKG NADPH oxidase (NOX) [67.Kalyanaraman al.Protein reverses osteoblast bone formation male diabetes.Diabetes. 67: 607-623Crossref (14) otherwise would contribute inflammation. If mirrored COVID-19, NRF2/HO-1 holds promise mitigating An important limitation development effective therapies SARS-Cov-2 poor reproducibility do relevant physiology,
Language: Английский
Citations
216
Antioxidants, Journal Year: 2023, Volume and Issue: 12(3), P. 651 - 651
Published: March 6, 2023
Aging is a complex biological process accompanied by progressive decline in the physical function of organism and an increased risk age-related chronic diseases such as cardiovascular diseases, cancer, neurodegenerative diseases. Studies have established that there exist nine hallmarks aging process, including (i) telomere shortening, (ii) genomic instability, (iii) epigenetic modifications, (iv) mitochondrial dysfunction, (v) loss proteostasis, (vi) dysregulated nutrient sensing, (vii) stem cell exhaustion, (viii) cellular senescence, (ix) altered communication. All these alterations been linked to sustained systemic inflammation, mechanisms contribute timing not clearly determined yet. Nevertheless, dysfunction one most important contributing process. Mitochondria primary endogenous source reactive oxygen species (ROS). During ATP production elevated ROS together with antioxidant defense. Elevated levels can cause oxidative stress severe damage cell, organelle membranes, DNA, lipids, proteins. This contributes phenotype. In this review, we summarize recent advances emphasis on production.
Language: Английский
Citations
204
Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 92, P. 10 - 24
Published: Nov. 10, 2020
Language: Английский
Citations
176
Heliyon, Journal Year: 2020, Volume and Issue: 6(5), P. e04107 - e04107
Published: May 1, 2020
Aging is a degenerative, biological, time-dependent, universally conserved process thus designed as one of the highest known risk factors for morbidity and mortality. Every individual has its own aging mechanisms both environmental conditions (75%) genetics (25%) account aging. Several theories have been proposed until now but not even single theory solves this mystery. There are still some queries un-answered to scientific community regarding behind However, oxidative stress (OST) considered famous that sees mitochondria leading organelles which largely contribute process. Many reactive oxygen species (ROS) produced endogenously exogenously associated with But mitochondrial ROS dysfunction due contributors toward Although damage cell machinery, new evidence suggests their role in signal transduction regulate biological physiological processes. Moreover, besides mitochondria, other important such peroxisome endoplasmic reticulum also produce nature provided humans free radical scavengers called antioxidants protect from harmful effects ROS. Future predictions aging, biochemical involved, biomarkers internal external can be easily done machine learning algorithms computational models. This review explains aspects contribution producing importance fighting against ROS, different models developed understand complexities
Language: Английский
Citations
168
Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 67, P. 101268 - 101268
Published: Feb. 6, 2021
Language: Английский
Citations
156