Advances in the Regulation of Inflammatory Mediators in Nitric Oxide Synthase: Implications for Disease Modulation and Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1204 - 1204

Published: Jan. 30, 2025

Nitric oxide synthases (NOS) are crucial enzymes responsible for the production of nitric (NO), a signaling molecule with essential roles in vascular regulation, immune defense, and neurotransmission. The three NOS isoforms, endothelial (eNOS), neuronal (nNOS), inducible (iNOS), tightly regulated by inflammatory mediators cellular pathways. While physiological NO is vital maintaining homeostasis, dysregulated activity contributes to pathogenesis numerous diseases, including cardiovascular disorders, neurodegenerative conditions, cancer. Recent advances understanding molecular mechanisms regulation have unveiled novel therapeutic opportunities, isoform-specific modulators, upstream pathways, nanotechnology-enhanced delivery systems. This review highlights these advancements, offering insights into how targeting its regulatory network can enable precise effective strategies managing inflammation-driven pathologies.

Language: Английский

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Linking oxidative stress biomarkers to disease progression and antioxidant therapy in hypertension and diabetes mellitus

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: May 26, 2025

Oxidative stress (OS) is increasingly recognized as a key factor linking hypertension (HTN) and diabetes mellitus (DM). This review summarizes recent evidence regarding the dual role of OS both an instigator amplifier cardiometabolic dysfunction. In HTN, reactive oxygen species (ROS) produced by NADPH oxidases (NOXs) mitochondrial dysfunction contribute to endothelial impairment vascular remodeling. DM, hyperglycemia-induced ROS production worsens beta-cell failure insulin resistance through pathways such AGE-RAGE signaling, protein kinase C (PKC) activation, polyol pathway. Clinically validated biomarkers OS, F2-isoprostanes (which indicate lipid peroxidation), 8-OHdG indicates DNA damage), activities redox enzymes like superoxide dismutase (SOD) glutathione peroxidase (GPx), show strong correlations with disease progression end-organ complications. Despite promising preclinical results, application antioxidant therapies in clinical settings has faced challenges due inconsistent outcomes, highlighting need for targeted approaches. Emerging strategies include: 1. Mitochondria-targeted antioxidants enhance function resistant HTN; 2. Nrf2 activators restore balance early diabetes; 3. Specific inhibitors NOX isoforms. We emphasize three transformative areas research: (i) interaction between microbiome ROS, where modifying gut microbiota can reduce systemic OS; (ii) use nanotechnology deliver directly pancreatic islets or atherosclerotic plaques; (iii) phenotype-specific diagnosis therapy guided genetic profiling (for example, KEAP1/NRF2 polymorphisms). Integrating these advances lifestyle modifications, following Mediterranean diet exercising regularly, may provide additional benefits. outlines mechanistic framework targeting comorbidity HTN DM while identifying critical knowledge gaps, particularly timing signaling development personalized medicine, which serve reference researchers clinicians working this area.

Language: Английский

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Subcellular Localization Guides eNOS Function

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13402 - 13402

Published: Dec. 13, 2024

Nitric oxide synthases (NOS) are enzymes responsible for the cellular production of nitric (NO), a highly reactive signaling molecule involved in important physiological and pathological processes. Given its remarkable capacity to diffuse across membranes, NO cannot be stored inside cells thus requires multiple controlling mechanisms regulate biological functions. In particular, regulation endothelial synthase (eNOS) activity has been shown crucial vascular homeostasis, primarily affecting cardiovascular disease other pathophysiological processes importance human health. Among factors, subcellular localization eNOS plays an role regulating enzymatic bioavailability NO. The aim this review is summarize pioneering studies more recent publications, unveiling some factors that influence compartmentalization discussing their functional implications health disease.

Language: Английский

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