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Relationship between oxidative stress and nuclear factor-erythroid-2-related factor 2 signaling in diabetic
Xia Wu1,2, Leitao Huang3, Jichun Liu1,2
1Department of Pharmacy, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Abstract:
Diabetic cardiomyopathy (DCM) is the leading cause of death worldwide, and oxidative stress was discovered to serve an important role in the pathophysiology of the condition. An imbalance between free radicals and antioxidant defenses is known to be associated with cellular dysfunction, leading to the development of various types of cardiac disease. Nuclear factor-erythroid-2-related factor 2 (NRF2) is a transcription factor that controls the basal and inducible expression levels of various antioxidant genes and other cytoprotective phase II detoxifying enzymes, which are ubiquitously expressed in the cardiac system. Kelch-like ECH-associated protein 1 (Keap1) serves as the main intracellular regulator of NRF2. Emerging evidence has revealed that NRF2 is a critical regulator of cardiac homeostasis via the suppression of oxidative stress. The activation of NRF2 was discovered to enhance specific endogenous antioxidant defense factors, one of which is antioxidant response element (ARE), which was subsequently illustrated to detoxify and counteract oxidative stress-associated DCM. The NRF2 signaling pathway is closely associated with the development of various types of cardiac disease, including ischemic heart disease, heart failure, myocardial infarction, atrial fibrillation and myocarditis. Therefore, it is hypothesized that drugs targeting this pathway may be developed to inhibit the activation of NRF2 signaling, thereby preventing the occurrence of DCM and effectively treating the disease.
Insights
Diabetic cardiomyopathy (DCM) involves oxidative stress. Activating the Nuclear factor-erythroid-2-related factor 2 (NRF2) pathway enhances antioxidant defenses, offering a potential therapeutic strategy for DCM.
Area of Science:
- Biochemistry
- Cardiology
- Molecular Biology
Background:
- Diabetic cardiomyopathy (DCM) is a major global health concern, significantly linked to oxidative stress.
- Oxidative stress, an imbalance between free radicals and antioxidant defenses, drives cellular dysfunction and cardiac disease.
- Nuclear factor-erythroid-2-related factor 2 (NRF2) is a key transcription factor regulating antioxidant and detoxification genes in the heart.
Purpose of the Study:
- To explore the role of the NRF2 signaling pathway in the pathophysiology of diabetic cardiomyopathy.
- To investigate the potential of targeting NRF2 for the prevention and treatment of DCM.
Main Methods:
- Review of existing literature on NRF2, Keap1, and their role in oxidative stress and cardiac homeostasis.
- Analysis of the NRF2-antioxidant response element (ARE) pathway's involvement in counteracting oxidative stress-induced cardiac dysfunction.
- Examination of the association between NRF2 pathway dysregulation and various cardiac diseases.
Main Results:
- NRF2 is a critical regulator of cardiac homeostasis, suppressing oxidative stress.
- Activation of NRF2 enhances endogenous antioxidant defenses, including the antioxidant response element (ARE).
- The NRF2 pathway is implicated in the development of multiple cardiac conditions, such as heart failure and myocardial infarction.
Conclusions:
- The NRF2 signaling pathway plays a crucial role in mitigating oxidative stress in diabetic cardiomyopathy.
- Targeting the NRF2 pathway presents a promising therapeutic avenue for preventing and treating DCM.
- Further research into NRF2-activating drugs could lead to novel treatments for oxidative stress-related cardiac diseases.
