Nrf2 Regulates Oxidative Stress and Its Role in Cerebral Ischemic Stroke

Antioxidants, Journal Year: 2022, Volume and Issue: 11(12), P. 2377 - 2377

Published: Nov. 30, 2022

Cerebral ischemic stroke is characterized by acute ischemia in a certain part of the brain, which leads to brain cells necrosis, apoptosis, ferroptosis, pyroptosis, etc. At present, there are limited effective clinical treatments for cerebral stroke, and recovery blood circulation will lead ischemia-reperfusion injury (CIRI). involves many pathological processes such as oxidative stress, inflammation, mitochondrial dysfunction. Nuclear factor erythroid 2-related 2 (Nrf2), one most critical antioxidant transcription factors cells, can coordinate various cytoprotective inhibit stress. Targeting Nrf2 considered potential strategy prevent treat injury. During ischemia, participates signaling pathways Keap1, PI3K/AKT, MAPK, NF-κB, HO-1, then alleviates or CIRI inhibiting anti-inflammation, maintaining homeostasis, protecting blood–brain barrier, ferroptosis. In this review, we have discussed structure Nrf2, mechanisms related research on treatment through pathway recent years, expounded important role future stroke.

Language: Английский

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Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation

Antioxidants, Journal Year: 2021, Volume and Issue: 10(12), P. 1859 - 1859

Published: Nov. 23, 2021

Oxidative stress is a pathological condition occurring due to an imbalance between the oxidants and antioxidant defense systems in body. Nuclear factor E2-related 2 (NRF2), encoded by gene NFE2L2, master regulator of phase II enzymes that protect against oxidative inflammation. NRF2/ARE signaling has been considered as promising target stress-mediated diseases like diabetes, fibrosis, neurotoxicity, cancer. The consumption dietary phytochemicals acts effective modulator various acute chronic diseases. In present review, we discussed role NRF2 Alzheimer’s disease (AD), Parkinson’s (PD), cancer, atherosclerosis. Additionally, curcumin, quercetin, resveratrol, epigallocatechin gallate, apigenin, sulforaphane, ursolic acid have effectively modified prevented both vitro vivo models. Based on literature, it clear can prevent (1) blocking stress-inhibiting inflammatory mediators through inhibiting Keap1 or activating Nrf2 expression its downstream targets nucleus, including HO-1, SOD, CAT; (2) regulating kinases GSK3beta, PI3/AKT, MAPK; (3) modifying epigenetic modulation, such methylation, at promoter region; however, further investigation into other upstream molecules effect them still need be investigated near future.

Language: Английский

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Superoxide Dismutase Administration: A Review of Proposed Human Uses

Molecules, Journal Year: 2021, Volume and Issue: 26(7), P. 1844 - 1844

Published: March 25, 2021

Superoxide dismutases (SODs) are metalloenzymes that play a major role in antioxidant defense against oxidative stress the body. SOD supplementation may therefore trigger endogenous machinery for neutralization of free-radical excess and be used variety pathological settings. This paper aimed to provide an extensive review possible uses SODs range settings, as well describe current pitfalls delivery strategies development solve bioavailability issues. We carried out PubMed query, using keywords “SOD”, “SOD mimetics”, supplementation”, which included papers published English language, between 2012 2020, on potential therapeutic applications SODs, including detoxification strategies. As highlighted this paper, it can argued generic effects beneficial under all tested conditions, from ocular cardiovascular diseases neurodegenerative disorders metabolic diseases, diabetes its complications obesity. However, must underlined clinical evidence efficacy is limited consequently, currently far being demonstrated.

Language: Английский

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Targeting ferroptosis suppresses osteocyte glucolipotoxicity and alleviates diabetic osteoporosis

Bone Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: March 9, 2022

Diabetic osteoporosis (DOP) is the leading complication continuously threatening bone health of patients with diabetes. A key pathogenic factor in DOP loss osteocyte viability. However, mechanism death remains unclear. Here, we identified ferroptosis, which iron-dependent programmed cell death, as a critical murine models DOP. The diabetic microenvironment significantly enhanced ferroptosis vitro, shown by substantial lipid peroxidation, iron overload, and aberrant activation pathway. RNA sequencing showed that heme oxygenase-1 (HO-1) expression was notably upregulated ferroptotic osteocytes. Further findings revealed HO-1 essential for its promoter activity controlled interaction between upstream NRF2 c-JUN transcription factors. Targeting or efficiently rescued disrupting vicious cycle peroxidation activation, eventually ameliorating trabecular deterioration. Our study provides insight into pathogenesis, our results provide mechanism-based strategy clinical treatment.

Language: Английский

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Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders

Antioxidants, Journal Year: 2022, Volume and Issue: 11(3), P. 555 - 555

Published: March 15, 2022

The heme oxygenase (HO) enzyme system catabolizes to carbon monoxide (CO), ferrous iron, and biliverdin-IXα (BV), which is reduced bilirubin-IXα (BR) by biliverdin reductase (BVR). HO activity represented two distinct isozymes, the inducible form, HO-1, a constitutive HO-2, encoded genes (HMOX1, HMOX2, respectively). HO-1 responds transcriptional activation in response wide variety of chemical physical stimuli, including its natural substrate heme, oxidants, phytochemical antioxidants. expression regulated NF-E2-related factor-2 counter-regulated Bach-1, heme-sensitive manner. Additionally, HMOX1 promoter polymorphisms have been associated with human disease. induction can confer protection inflammatory conditions through removal pro-oxidant potential catalyst lipid peroxidation, whereas iron released from may trigger ferritin synthesis or ferroptosis. production heme-derived reaction products (i.e., BV, BR) contribute HO-dependent cytoprotection via antioxidant immunomodulatory effects. BVR BR newly recognized roles regulation. CO alter mitochondrial function leading modulation downstream signaling pathways that culminate anti-apoptotic, anti-inflammatory, anti-proliferative This review will present evidence for beneficial effects diseases, cardiovascular disease (CVD), metabolic conditions, diabetes obesity, as well acute chronic diseases liver, kidney, lung. Strategies targeting pathway, genetic expression, application BR, gas, donor compounds show therapeutic organ ischemia/reperfusion injury. Evidence studies indicate represent biomarker oxidative stress various clinical while increases serum levels correlated inversely risk CVD Ongoing trials investigate

Language: Английский

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