Aims: Haem oxygenase-1 (HO-1) is a haem-degrading enzyme that generates carbon monoxide, bilirubin, and iron ions. Through these compounds, HO-1 mitigates cellular injury by exerting antioxidant, anti-apoptotic, and anti-inflammatory effects. Here, we examined the influence of HO-1 deficiency and transient hypoxia/ischaemia-induced HO-1 overexpression on post-injury hindlimb recovery.
Methods And Results: Mice lacking functional HO-1 (HO-1(-/-)) showed reduced reparative neovascularization in ischaemic skeletal muscles, impaired blood flow (BF) recovery, and increased muscle cell death compared with their wild-type littermates. Human microvascular endothelial cells (HMEC-1) transfected with plasmid vector (pHRE-HO-1) carrying human HO-1 driven by three hypoxia response elements (HREs) and cultured in 0.5% oxygen demonstrated markedly increased expression of HO-1. Such upregulated HO-1 levels were effective in conferring protection against H(2)O(2)-induced cell death and in promoting the proangiogenic phenotype of HMEC-1 cells. More importantly, when delivered in vivo, pHRE-HO-1 significantly improved the post-ischaemic foot BF in mice subjected to femoral artery ligation. These effects were associated with reduced levels of pro-inflammatory cytokines (IL-6 and CXCL1) and lower numbers of transferase-mediated dUTP nick-end labelling-positive cells. Moreover, HO-1 delivered into mouse skeletal muscles seems to influence the regenerative potential of myocytes as it significantly changed the expression of transcriptional (Pax7, MyoD, myogenin) and post-transcriptional (miR-146a, miR-206) regulators of skeletal muscle regeneration.
Conclusion: Our results suggest the therapeutic potential of HO-1 for prevention of adverse effects in critical limb ischaemia.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527762 | PMC |
| http://dx.doi.org/10.1093/cvr/cvs284 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Kurarinone Mitigates LPS-Induced Inflammatory Osteolysis by Inhibiting Osteoclastogenesis Through the Reduction of ROS Levels and Suppression of the PI3K/AKT Signaling Pathway.
Inflammation
January 2025
The Key Laboratory of Spine and Spinal Cord Disease of Jiangxi Province, Nanchang, 330006, China.
Inflammatory bone resorption represents a pathological condition marked by an increase in bone loss, commonly associated with chronic inflammatory conditions such as rheumatoid arthritis and periodontitis. Current therapies primarily focus on anti-inflammatory drugs and bisphosphonates; however, these treatments are limited due to side effects, inadequate efficacy, and unpredictable long-term complications. Kurarinone (KR), a bioactive compound isolated from the traditional Chinese herb Sophora flavescens, exhibits a range of biological activities, including anti-inflammatory, anticancer, and cardiovascular protective effects.
View Article and Find Full Text PDFScopoletin alleviates acetaminophen-induced hepatotoxicity through modulation of NLRP3 inflammasome activation and Nrf2/HMGB1/TLR4/NF-κB signaling pathway.
Int Immunopharmacol
January 2025
Key Laboratory of Natural Medicines of Changbai Mountain, Ministry of Education, Yanbian University, Yanji, Jilin 133002, China. Electronic address:
Scopoleitin (SP), a bioactive compound from many edible plants and fruits, exerts a wide range of biological activities, however the role and mechanism of SP in acetaminophen (APAP)-induced hepatotoxicity remains unclear. In this study, we verified the protective effect of SP on APAP-induced liver injury (AILI) hepatotoxicity and explore the underlying molecular mechanisms. Here, we showed that SP alleviated AILI by reducing serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, hepatic histopathological damage, inflammation, and liver cell apoptosis.
View Article and Find Full Text PDFBackgrounds: Abuse of feed supplement can cause oxidative stress and inflammatory responses in Gallus gallus. Synbiotics are composed of prebiotics and probiotics and it possess huge application potentials in the treatment of animal diseases.
Methods: This study examined the effect of d-tagatose on the probiotic properties of L.
Acute anticonvulsant effects of dapsone on PTZ- and MES-induced seizures in mice: NLRP3 inflammasome inhibition and Nrf2/HO-1 pathway preservation.
Pharmacol Rep
January 2025
Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran.
Background: Epilepsy, a neurological disorder characterized by recurrent seizures, presents considerable difficulties in treatment, particularly when dealing with drug-resistant cases. Dapsone, recognized for its anti-inflammatory properties, holds promise as a potential therapeutic option. However, its effectiveness in epilepsy requires further investigation.
View Article and Find Full Text PDFGlioprotective Effects of Resveratrol Against Glutamate-Induced Cellular Dysfunction: The Role of Heme Oxygenase 1 Pathway.
Neurotox Res
January 2025
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Resveratrol, a natural polyphenol, has shown promising neuroprotective effects in several in vivo and in vitro experimental models. However, the mechanisms by which resveratrol mediates these effects are not fully understood. Glutamate is the major excitatory neurotransmitter in the brain; however, excessive extracellular glutamate levels can affect neural activity in several neurological diseases.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!