The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 187 - 187

Published: Feb. 6, 2025

Heme oxygenase (HO) metabolizes heme into ferrous iron, carbon monoxide (CO), and biliverdin-IXα (BV), the latter being reduced bilirubin-IXα (BR) by biliverdin reductase-A (BVR). exists as two isoforms, HO-1, inducible involved in cell stress response, HO-2, constitutive committed to physiologic turnover of intracellular oxygen sensing. Many studies have identified genetic variants HO/BVR system suggested their connection free radical-induced diseases. The most common include (GT)n dinucleotide length polymorphisms single nucleotide polymorphisms. Gain-of-function mutations HO-1 HO-2 genes foster ventilator response hypoxia reduce risk coronary heart disease age-related macular degeneration but increase neonatal jaundice, sickle disease, Parkinson’s disease. Conversely, loss-of-function gene type 2 diabetes mellitus, chronic obstructive pulmonary some types cancers. Regarding BVR, reported green jaundice. Unfortunately, physiological role does not allow for hypothesis silencing/induction strategies, knowledge these can certainly facilitate a medical approach that enables early diagnoses tailored treatments.

Language: Английский

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Heme oxygenase-1 orchestrates the immunosuppressive program of tumor-associated macrophages

JCI Insight, Journal Year: 2020, Volume and Issue: unknown

Published: May 5, 2020

Tumor-associated macrophages (TAMs) contribute to the maintenance of a strong immunosuppressive environment, supporting tumor progression and resistance treatment. To date, mechanisms that drive acquisition these features are still poorly defined. Heme oxygenase-1 (HO-1) is rate-limiting enzyme catabolizes free heme. It displays important cytoprotective, antiinflammatory, antioxidant properties. A growing body evidence suggests HO-1 may also promote development. Herein, we show highly expressed in monocytic cells microenvironment (TME) once they differentiate into TAMs. Deletion myeloid compartment enhances beneficial effects therapeutic antitumor vaccine by restoring CD8+ T cell proliferation cytotoxicity. We further induction plays major role monocyte education modulating their transcriptional epigenetic programs. These results identify as valuable target reprogram TME synergize with current cancer therapies facilitate response.

Language: Английский

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Pharmacological Applications of Nrf2 Inhibitors as Potential Antineoplastic Drugs

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(8), P. 2025 - 2025

Published: April 24, 2019

Oxidative stress (OS) is associated with many diseases ranging from cancer to neurodegenerative disorders. Nuclear factor-erythroid 2 p45-related factor (Nrf2) one of the most effective cytoprotective controller against OS. Modulation Nrf2 pathway constitutes a remarkable strategy in antineoplastic treatments. A big number Nrf2-antioxidant response element activators have been screened for use as chemo-preventive drugs OS like even though activation happens variety cancers. Research proved that hyperactivation produces situation helps survival normal well malignant cells, protecting them OS, anticancer drugs, and radiotherapy. In this review, modulation pathway, activity challenges development an Nrf2-based anti-cancer treatment approaches are discussed.

Language: Английский

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Clinical Significance of Heme Oxygenase 1 in Tumor Progression

Antioxidants, Journal Year: 2021, Volume and Issue: 10(5), P. 789 - 789

Published: May 17, 2021

Heme oxygenase 1 (HO-1) plays a key role in cell adaptation to stressors through the antioxidant, antiapoptotic, and anti-inflammatory properties of its metabolic products. For these reasons, cancer cells, HO-1 can favor aggressiveness resistance therapies, leading poor prognosis/outcome. Genetic polymorphisms promoter have been associated with an increased risk progression high degree therapy failure. Moreover, evidence from biopsies highlights possible correlation between expression, pathological features, clinical outcome. Indeed, levels tumor specimens often correlate reduced survival rates. Furthermore, modulation has proposed order improve efficacy antitumor therapies. However, contrasting on biology reported. This review focuses as promising biomarker progression; understanding data might guide therapeutic choice outcome patients terms prognosis life quality.

Language: Английский

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NRF2 and Key Transcriptional Targets in Melanoma Redox Manipulation

Cancers, Journal Year: 2022, Volume and Issue: 14(6), P. 1531 - 1531

Published: March 16, 2022

Melanocytes are dendritic, pigment-producing cells located in the skin and responsible for its protection against deleterious effects of solar ultraviolet radiation (UVR), which include DNA damage elevated reactive oxygen species (ROS). They do so by synthesizing photoprotective melanin pigments distributing them to adjacent (e.g., keratinocytes). However, melanocytes encounter a large burden oxidative stress during this process, due both exogenous endogenous sources. Therefore, employ numerous antioxidant defenses protect themselves; these largely regulated master response transcription factor, nuclear factor erythroid 2-related 2 (NRF2). Key effector transcriptional targets NRF2 components glutathione thioredoxin systems. Despite defenses, melanocyte often is subject mutations that result dysregulation proliferative mitogen-activated protein kinase (MAPK) pathway cell cycle. Following tumor initiation, systems co-opted, consequence caused metabolic reprogramming, establish an altered redox homeostasis. This homeostasis contributes progression metastasis, while also complicating application treatments. Further understanding homeostasis, presence or absence disease, would contribute development novel therapies aid prevention treatment melanomas other diseases

Language: Английский

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