Annexin A5 ameliorates traumatic brain injury-induced neuroinflammation and neuronal ferroptosis by modulating the NF-ĸB/HMGB1 and Nrf2/HO-1 pathways

Gao, Yalong; Zhang, Hejun; Wang, Jiwei; Li, Fanjian; Li, Xiaotian; Li, Tuo; Li, Lei; Peng, Ruilong; Liu, Li; Cui, Weiyun; Zhang, Shu; Zhang, Jianning

doi:10.1016/j.intimp.2022.109619

Cited by 17 publications

(10 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous attention to AnxA5 function has mostly focused on its anti-in ammatory ability [33][34][35][36]. The ipping of PS from the inner to the outer cell membrane signi cantly occurs when cells are damaged, which subsequently recruits platelets and leukocytes, leading to thrombus formation and in ammation.…”

Section: Discussionmentioning

confidence: 99%

Annexin-A5 monomer as a membrane repair agent for the treatment of renal ischemia-reperfusion injury

Dong,

Jia,

Kang

et al. 2024

Mol Biol Rep

View full text Add to dashboard Cite

Background: Renal ischemia-reperfusion injury (IRI) is one of the causes of acute kidney injury. Annexin A5 (AnxA5) as a calcium-dependent cell membrane binding protein has shown good protective effects in various organ IRI models. This study explored the therapeutic effect of exogenous AnxA5 monomer protein on renal IRI and its potential mechanism.Methods: In vivo, different doses of AnxA5 were injected intravenously to treat bilateral renal IRI models in SD rats. This model con rms the protective effect of AnxA5 on the structure and function of the kidneys. In vitro, HK-2, the renal tubular epithelial cells, was subjected to hypoxia for 12 hours, followed by restoration of normal oxygen supply to simulate IRI. In vitro experiments have demonstrated the mechanism of action of AnxA5 by measuring cell activity and permeability. The comparison of the mutant AnxA5 protein M23 and the application of calcium-free culture medium further validated the protective effect of AnxA5 by forming a network structure.Results: In vivo, AnxA5 monomer improved kidney function damage caused by IRI and prevented the deterioration of the pathological structure. In vitro, AnxA5 protected cell viability, reduced cell membrane permeability, and inhibited cell apoptosis induced by IRI treatment. However, AnxA5 lost its protective effect in the calcium-free culture medium and the M23 that lack the ability of forming a two-dimensional network structure could not reduce cell membrane permeability and lost its protective effect on cell viability, indicating that the formation of a two-dimensional network structure of AnxA5 is critical to the repair of the cell membrane.Conclusions: Exogenous AnxA5 monomer could prevent renal IRI by binding to the damaged renal tubular epithelial cell membrane, forming a two-dimensional network structure to maintain cell membrane integrity, and ultimately prevent cell death.

show abstract

Section: Discussionmentioning

confidence: 99%

Annexin-A5 monomer as a membrane repair agent for the treatment of renal ischemia-reperfusion injury

Dong,

Jia,

Kang

et al. 2024

Mol Biol Rep

View full text Add to dashboard Cite

show abstract

“…Furthermore, HMGB1 overexpression was found to reverse the role of SA in protecting C2C12 cells from H/R. In traumatic brain injury, Gao et al has highlighted that HGMB1‐mediated ROS is required for the occurrence of ferroptosis (Gao et al, 2023). Knockdown of HMGB1 has been reported to suppress glucose‐induced ferroptosis of mesangial cells by activating Nrf2 (Wu et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Syringic acid suppresses ferroptosis of skeletal muscle cells to alleviate lower limb ischemia/reperfusion injury in mice via the HMGB1 pathway

Wang,

Qi,

Gao

et al. 2023

Chem Biol Drug Des

View full text Add to dashboard Cite

Ischemia/reperfusion (I/R) of skeletal muscle in the lower limbs is an important factor affecting the outcome of lower limbs ischemia patients, with no effective preventive or therapeutic approaches available. The study was to investigate the effect of syringic acid (SA) on I/R skeletal muscle in the lower limbs injury. Mice femoral artery I/R models and C2C12 cell hypoxia/reoxygenation (H/R) models was establish, tissue damage, inflammatory status, and high mobility group box 1 (HMGB1) pathway were evaluated using histological analysis, enzyme‐linked immunosorbent assay, and western blotting. Further, the study detected the effect of SA on cell apoptosis, lipid peroxidation, Fe2+ level, and ferroptosis‐related proteins expression. Finally, the effect of HMGB1 expression on SA in H/R stimulation was studied. SA alleviated pathological damage and reduced levels of IL‐1β, IL‐6, and TNF‐α in muscle tissues from femoral artery I/R mouse models. SA upregulated Bcl‐2 and SOD as well as downregulated Bax, MDA, TBARS content, and Fe2+ level in H/R‐induced cells. SA inhibited HMGB1 expression and promoted Nrf2, HO‐1, GPX4, and SLC7A11 expressions in the injured tissues and cells. Such effects of SA on H/R‐induced cells were rescued by HMGB1 overexpression. SA suppressed ferroptosis of skeletal muscle cells to alleviate lower limb I/R injury in mice by blocking the HMGB1 pathway, providing new insights for the treatment of lower limb ischemia–reperfusion injury.

show abstract

“…In addition, heme oxygenase HO-1, the main regulatory enzyme of Nrf2, is believed to reduce NF-κB activity [118]. Annexin A5 facilitates phenotype transformation of microglia via the Nrf2 pathway to NF-κB, counteracting the inflammatory response, ferroptosis, and oxidative stress, thereby improving neurocognitive dysfunction [119]. The effect of Nrf2 on neuroinflammation heavily relies on NF-κB, but the mechanisms by which Nrf2 regulates NF-κB are varied.…”

Section: Nrf2mentioning

confidence: 99%

“…Interestingly, the well-known ferroptosis inhibitor Fer-1 and its analogue Srs11-92 were able to reverse this phenomenon [129]. Notably, annexin A5, an annexin protein, has been shown to mitigate inflammation and ferroptosis following traumatic brain injury by targeting both the HMGB1/NF-κB pathway and the Nrf2 pathway [119].…”

Section: Nf-κbmentioning

confidence: 99%

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

Xu,

Jia,

et al. 2024

Antioxidants

View full text Add to dashboard Cite

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain diseases, traumatic brain injury, epilepsy, depression, and more. The involved pathogenesis is notably intricate and diverse. Ferroptosis and neuroinflammation play pivotal roles in elucidating the causes of cognitive impairment stemming from these diseases. Given the concurrent occurrence of ferroptosis and neuroinflammation due to metabolic shifts such as iron and ROS, as well as their critical roles in central nervous disorders, the investigation into the co-regulatory mechanism of ferroptosis and neuroinflammation has emerged as a prominent area of research. This paper delves into the mechanisms of ferroptosis and neuroinflammation in central nervous disorders, along with their interrelationship. It specifically emphasizes the core molecules within the shared pathways governing ferroptosis and neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, and how different immune cells and structures contribute to cognitive dysfunction through these mechanisms. Researchers’ findings suggest that ferroptosis and neuroinflammation mutually promote each other and may represent key factors in the progression of central neurological disorders. A deeper comprehension of the common pathway between cellular ferroptosis and neuroinflammation holds promise for improving symptoms and prognosis related to central neurological disorders.

show abstract

Annexin A5 ameliorates traumatic brain injury-induced neuroinflammation and neuronal ferroptosis by modulating the NF-ĸB/HMGB1 and Nrf2/HO-1 pathways

Cited by 17 publications

References 41 publications

Annexin-A5 monomer as a membrane repair agent for the treatment of renal ischemia-reperfusion injury

Annexin-A5 monomer as a membrane repair agent for the treatment of renal ischemia-reperfusion injury

Syringic acid suppresses ferroptosis of skeletal muscle cells to alleviate lower limb ischemia/reperfusion injury in mice via the HMGB1 pathway

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

Contact Info

Product

Resources

About