The Antioxidant Transcription Factor Nrf2 in Cardiac Ischemia–Reperfusion Injury

Mata, Ana M.; Cadenas, Susana

doi:10.3390/ijms222111939

Cited by 44 publications

(26 citation statements)

References 233 publications

(290 reference statements)

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“…Besides the liver, these Nrf2‐mediated antioxidant mechanisms have also been described during IR in the brain [58–60], heart [61–63], and kidney [64–66].…”

Section: Nrf2 As a Transcription Factor: Cellular And Molecular Funct...mentioning

confidence: 99%

Nrf2 and oxidative stress in liver ischemia/reperfusion injury

et al. 2022

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In response to stress signal, nuclear factor‐erythroid 2‐related factor 2 (Nrf2) induces the expression of target genes involved in antioxidant defense and detoxification. Nrf2 activity is strictly regulated through a variety of mechanisms, including regulation of Keap1‐Nrf2 stability, transcriptional regulation (NF‐ĸB, ATF3, ATF4), and post‐transcriptional regulation (miRNA), evidencing that transcriptional responses of Nrf2 are critical for the maintenance of homeostasis. Ischemia‐reperfusion (IR) injury is a major cause of graft loss and dysfunction in clinical transplantation and organ resection. During the IR process, the generation of reactive oxygen species (ROS) leads to damage from oxidative stress, oxidation of biomolecules, and mitochondrial dysfunction. Oxidative stress can trigger apoptotic and necrotic cell death. Stress factors also result in the assembly of the inflammasome protein complex and the subsequent activation and secretion of proinflammatory cytokines. After Nrf2 activation, the downstream antioxidant upregulation can act as a primary cellular defense against the cytotoxic effects of oxidative stress and help to promote hepatic recovery during IR. The complex crosstalk between Nrf2 and cellular pathways in liver IR injury and the potential therapeutic target of the Nrf2 inducers will be discussed in the present review.

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“…Besides the liver, these Nrf2‐mediated antioxidant mechanisms have also been described during IR in the brain [58–60], heart [61–63], and kidney [64–66].…”

Section: Nrf2 As a Transcription Factor: Cellular And Molecular Funct...mentioning

confidence: 99%

Nrf2 and oxidative stress in liver ischemia/reperfusion injury

et al. 2022

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“…Keap1 is a polypeptide composed of 624 amino acid residues and 5 domains: NTR (N-terminus), IVR, BTB/POZ DGR, and CTR (C-terminus). Scientific research established in cell lines and animal models that Nrf2/Keap1 pathway activation exerts protective effects in ischemia–reperfusion injury in vessels [ 68 ].…”

Section: Nrf2mentioning

confidence: 99%

Oxidative Stress in Arterial Hypertension (HTN): The Nuclear Factor Erythroid Factor 2-Related Factor 2 (Nrf2) Pathway, Implications and Future Perspectives

et al. 2022

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Arterial hypertension (HTN) is one of the most prevalent entities globally, characterized by increased incidence and heterogeneous pathophysiology. Among possible etiologies, oxidative stress (OS) is currently extensively studied, with emerging evidence showing its involvement in endothelial dysfunction and in different cardiovascular diseases (CVD) such as HTN, as well as its potential as a therapeutic target. While there is a clear physiological equilibrium between reactive oxygen species (ROS) and antioxidants essential for many cellular functions, excessive levels of ROS lead to vascular cell impairment with decreased nitric oxide (NO) availability and vasoconstriction, which promotes HTN. On the other hand, transcription factors such as nuclear factor erythroid factor 2-related factor 2 (Nrf2) mediate antioxidant response pathways and maintain cellular reduction–oxidation homeostasis, exerting protective effects. In this review, we describe the relationship between OS and hypertension-induced endothelial dysfunction and the involvement and therapeutic potential of Nrf2 in HTN.

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“…Nrf2 is a transcription factor that controls cellular defense responses [ 199 ], particularly in the regulation of the expression of antioxidant and detoxification genes [ 199 , 200 , 201 ]. Nrf2 is known to protect cardiomyocytes against oxidative stress by increasing endogenous antioxidants [ 202 , 203 ].…”

Section: Modification Of I/r-induced Defects In Signal Transductionmentioning

confidence: 99%

“…In fact, several studies have shown that the activation of Nrf2 and the subsequent upregulation of antioxidant enzyme gene expression is an important mechanism of cardioprotection due to ischemic/hypoxic preconditioning, and that low concentrations of ROS may be an essential signal for the protective process [ 212 , 213 , 214 , 215 ]. Furthermore, Nrf2 has also been reported to modulate intracellular Ca 2+ levels [ 216 ], and thus cardioprotection against I/R injury due to the activation of Nrf2 has recently been explored for clinical applicability [ 199 ]. In addition, the role of Nrf2 signal transduction in the protective actions of IP has also been examined [ 212 , 217 ].…”

Section: Modification Of I/r-induced Defects In Signal Transductionmentioning

confidence: 99%

Modification of Ischemia/Reperfusion-Induced Alterations in Subcellular Organelles by Ischemic Preconditioning

Tappia

Shah

Ramjiawan

et al. 2022

IJMS

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It is now well established that ischemia/reperfusion (I/R) injury is associated with the compromised recovery of cardiac contractile function. Such an adverse effect of I/R injury in the heart is attributed to the development of oxidative stress and intracellular Ca2+-overload, which are known to induce remodeling of subcellular organelles such as sarcolemma, sarcoplasmic reticulum, mitochondria and myofibrils. However, repeated episodes of brief periods of ischemia followed by reperfusion or ischemic preconditioning (IP) have been shown to improve cardiac function and exert cardioprotective actions against the adverse effects of prolonged I/R injury. This protective action of IP in attenuating myocardial damage and subcellular remodeling is likely to be due to marked reductions in the occurrence of oxidative stress and intracellular Ca2+-overload in cardiomyocytes. In addition, the beneficial actions of IP have been attributed to the depression of proteolytic activities and inflammatory levels of cytokines as well as the activation of the nuclear factor erythroid factor 2-mediated signal transduction pathway. Accordingly, this review is intended to describe some of the changes in subcellular organelles, which are induced in cardiomyocytes by I/R for the occurrence of oxidative stress and intracellular Ca2+-overload and highlight some of the mechanisms for explaining the cardioprotective effects of IP.

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The Antioxidant Transcription Factor Nrf2 in Cardiac Ischemia–Reperfusion Injury

Cited by 44 publications

References 233 publications

Nrf2 and oxidative stress in liver ischemia/reperfusion injury

Nrf2 and oxidative stress in liver ischemia/reperfusion injury

Oxidative Stress in Arterial Hypertension (HTN): The Nuclear Factor Erythroid Factor 2-Related Factor 2 (Nrf2) Pathway, Implications and Future Perspectives

Modification of Ischemia/Reperfusion-Induced Alterations in Subcellular Organelles by Ischemic Preconditioning

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