Is Inducible Nitric Oxide Synthase (iNOS) Promising as a New Target Against Pulmonary Hypertension?

Antioxidants, Год журнала: 2025, Номер 14(4), С. 377 - 377

Опубликована: Март 21, 2025

Pulmonary hypertension (PH) is a progressive disease characterized by elevated blood pressure in the pulmonary arteries, associated also with inflammation and oxidative stress. Inducible nitric oxide synthase (iNOS) one of key mediators immune system activation. Although preclinical studies mostly suggest detrimental role iNOS overactivation PH, there lack exhaustive analyses summaries. Therefore, this literature overview aims to fill gap. The involvement pathogenesis four main clinical groups PH discussed assess whether targeting could be promising way treat PH. expression patterns organs primarily affected are analyzed both animals humans. Consequently, effectiveness pharmacological inhibition and/or gene deletion compared, reference activity constitutive NOS isoforms, particularly endothelial (eNOS). Overall, our suggests that selective inhibitors considered as novel treatment strategy for decreases right ventricular artery pressure, alleviation hypertrophy, improvements cardiac function were observed, among others. Nevertheless, further research efforts area needed.

Язык: Английский

---

Novel strategies to overcome chemoresistance in human glioblastoma

Biochemical Pharmacology, Год журнала: 2024, Номер unknown, С. 116588 - 116588

Опубликована: Окт. 1, 2024

Язык: Английский

---

NOS2 and COX-2 Co-Expression Promotes Cancer Progression: A Potential Target for Developing Agents to Prevent or Treat Highly Aggressive Breast Cancer

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 6103 - 6103

Опубликована: Июнь 1, 2024

Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding spatial distribution is essential for deciphering roles in diverse processes. This review establishes a framework the chemical biology of NO RNS, exploring dynamic reactions within context cancer. Concentration-dependent signaling reveals distinctive processes cancer, with three levels influencing oncogenic properties. In this context, plays crucial role cancer cell proliferation, metastasis, chemotherapy resistance, immune suppression. Increased NOS2 expression correlates poor survival across different tumors, including breast Additionally, can crosstalk proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote progression. COX-2 co-expression positive feed-forward loop, driving immunosuppression metastasis estrogen receptor-negative (ER-) Spatial evaluation orthogonal expression, suggesting unique these niches tumor microenvironment (TME). COX2 niche formation requires IFN-γ cytokine-releasing cells. These contribute clinical outcomes, emphasizing Strategies target markers include direct inhibition, involving pan-inhibitors selective inhibitors, as well indirect approaches targeting induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates inhibition offering therapeutic applications. Thus, understanding distribution, implications progression provides valuable insights developing targeted therapies preventive strategies.

Язык: Английский

---

The Role of Thioredoxin System in Shank3 Mouse Model of Autism

Journal of Molecular Neuroscience, Год журнала: 2024, Номер 74(4)

Опубликована: Сен. 30, 2024

Язык: Английский

---

The nitration of SIRT6 aggravates neuronal damage during cerebral ischemia-reperfusion in rat

Nitric Oxide, Год журнала: 2024, Номер 153, С. 26 - 40

Опубликована: Окт. 5, 2024

Язык: Английский

---

Shared early molecular mechanisms revealed in P301S and 5xFAD Alzheimer’s disease mouse models

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Март 26, 2025

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by early molecular events that influence progression. Still, mechanisms caused different mutations of AD are not understood. We have performed a multidisciplinary study to investigate and compare stages pathology in two transgenic mouse models: P301S 5xFAD. Using SNOTRAP-based mass spectrometry, we assessed changes S-nitrosylation, nitric oxide-mediated post-translational modification, proteins both models during their juvenile age. The increased levels 3-nitrotyrosine confirmed nitrosative stress mutant mice. Systems biology analysis revealed shared processes between models, particularly γ-aminobutyric acid (GABA)ergic glutamatergic neurotransmission processes. In model, identified 273 S-nitrosylated (SNOed) cortex, with 244 uniquely SNOed diseased 5xFAD 309 were identified. found altered expression glutamate/GABA-related markers cortex hippocampus models. Additionally, phosphorylation mTOR signaling components hyperactivation this pathway Conversely, mice showed no significant except for elevated ribosomal protein S6 cortex. Our findings key stages. These could serve as potential biomarkers therapeutic targets early-stage AD.

Язык: Английский

---

Blocking nitric oxide production for glioblastoma: A targeted therapeutic approach

Brain medicine :, Год журнала: 2025, Номер unknown, С. 1 - 9

Опубликована: Май 20, 2025

Glioblastoma (GBM) represents the foremost prevalent and aggressive form of primary brain tumor, characterized by high morbidity mortality rates. Nitric oxide (NO) has been shown to have diverse effects on various cancers, including GBM. Our previous study NO synthase (NOS) hyperactivation in GBM cell lines. survival was reversed NOS-targeting pharmacological inhibition vitro. The current work explores impact inducible neuronal NOS (iNOS nNOS) inhibitors, BA-103 BA-101, respectively, a glioblastoma xenograft model. Both agents mitigate nitrosative stress through distinct mechanisms. NOD-SCID mice were used establish subcutaneous tumor model with U-87 MG cells. BA-101 administered via intraperitoneal injections. Tumor metrics, weight volume, assessed. Immunofluorescence Western blots conducted assess stress, proliferation, death. Treatment particularly significantly reduced volume A dose-dependent identified 80 mg/kg as most efficacious dose for treatment. Combining antitumor drug temozolomide (TMZ) synergistically size increased survivability bearing TMZ-sensitive findings suggest that targeting nNOS holds promise therapeutic strategy

Язык: Английский

---

Nitric oxide protects intestinal mucosal barrier function and prevents acute graft rejection after intestinal transplantation: a mini-review

Nitric Oxide, Год журнала: 2024, Номер 149, С. 1 - 6

Опубликована: Май 26, 2024

Язык: Английский

---

A Novel Thioredoxin-Mediated Mechanism in Autism Spectrum Disorder

Опубликована: Янв. 1, 2024

Autism spectrum disorder (ASD) is a complex neurodevelopmental characterized by difficulties in social interaction and communication, repetitive behaviors, restricted interests. Over time, the prevalence of ASD increasing, reaching 2% population to date. Unfortunately, underlying molecular mechanism behind remains unknown. Therefore, there no FDA-approved drug for treatment, It has been reported that oxidative nitrosative stress are strongly linked ASD. We have recently found nitric oxide (NO•) NO•-meditated post-transitional modifications play key role One proteins affected affecting NO• thioredoxin (Trx). Here we show Trx antioxidant system may crucial pathology. hypothesize altered Shank3 KO mouse model autism, which lead decreased activity nuclear factor erythroid 2-related 2 (Nrf2), leading stress, thus, contributing ASD-related phenotypes. To test this hypothesis, conducted vivo behavioral studies used primary cortical neurons derived from mutant mice as well human SH-SY5Y with SHANK3 mutation. showed significant changes levels redox mice. A Trx1 inhibitor PX-12 Nrf2 expression wild-type mice, causing abnormal alterations synaptic neurotransmission markers, an elevation stress. The tests revealed inhibition results ASD-like phenotype, similar observed autism. Our findings confirm strong link between ASD, including increased oxidative/nitrosative impaired phenotype. study pave way developing new treatments.

Язык: Английский

---

Cloning and characterization of a novel Nitric oxide synthase gene from Exiguobacterium profundum and its expression in Escherichia coli

Protein Expression and Purification, Год журнала: 2024, Номер unknown, С. 106609 - 106609

Опубликована: Сен. 1, 2024

Язык: Английский

---