Nitric oxide (NO) is a key signalling molecule in endothelial cells, playing a complex role in the regulation of cell apoptosis. One of its critical molecular targets is cytochrome c (CytC), a heme protein whose oxidation state determines its function in mitochondrial respiration and cell death pathways. Using resonance Raman (RR) imaging with 405 nm excitation, we investigated NO-induced changes in the redox state of CytC in various endothelial cell lines. Calcium ionophore (A23187), known to activate endothelial NO synthase (eNOS), induced a shift in CytC from the ferrous (CytC-Fe^II) to ferric (CytC-Fe^III) state. This effect was cell type-dependent and most prominent in human aortic and dermal microvascular endothelial cells (HAECs, HMECs). The transition was prevented by L-NAME (NOS inhibitor), PEG-SOD (superoxide scavenger), and NecroX-5 (peroxynitrite scavenger), suggesting that ONOO^- plays a mediating role. Physiological NO inducers like VEGF and bradykinin also promoted CytC oxidation, but in a spatially distinct manner, suggesting subcellular specificity in NO signalling. Interestingly, applying an external NO donor (DEA-NONOate) did not trigger oxidation but briefly formed a CytC-Fe^II-NO complex. Despite mitochondrial membrane potential disturbances following A23187 treatment, no apoptosis was observed, indicating that CytC oxidation can be an early, reversible marker of mitochondrial stress rather than cell death. Our findings demonstrate the utility of RR imaging for real-time monitoring of CytC redox state and underscore the complexity of NO signalling in endothelial physiology and its potential implications for vascular health.

2025-04-01·INTERNATIONAL JOURNAL OF PHARMACEUTICS

Nanomedicine-enhanced SCAP hybrid spheroids: A novel approach for improved stem cell survival

Article

作者: Mwema, Ariane ; Haufroid, Vincent ; Delongie, Kevin-Alexandre ; des Rieux, Anne ; Ucakar, Bernard ; Vanvarenberg, Kevin ; Debuisson, Floriane

In regenerative medicine, the therapeutic potential of mesenchymal stem cells (MSC), such as stem cells from human apical papilla (SCAP), is well-documented and largely attributed to their secretome. However, their poor survival post-transplantation limits their efficacy. This study hypothesized that combining SCAP spheroids with nanomedicines loaded with NecroX-5 (an anti-necrotic drug) and rapamycin (an immunosuppressive agent) would enhance SCAP survival in vivo. The approach aimed to reduce oxidative stress-related cell death and suppress immune reactions towards xeno-/allogenic cells. Two types of nanocarriers, polymeric nanoparticles (NP) and lipid nanocapsules (LNC), were compared to encapsulate NecroX-5 and rapamycin. A magnetic-dependent method was employed to associate SCAP with nanomedicines, involving co-encapsulation of drugs and Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) in the nanocarriers and cell magnetization using Nanoshuttle™. In vivo, SCAP hybrid spheroids expressing Luciferase, when injected subcutaneously into immunocompetent mice, showed increased bioluminescence signals compared to regular spheroids. These results provide proof-of-concept that magnetic-driven association of cells and nanomedicines into hybrid spheroids is feasible and suggest that delivering SCAP as hybrid spheroids can enhance their survival.

2022-12-01·RESPIRATORY RESEARCH2区 · 医学

NecroX-5 ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3-mediated epithelial–mesenchymal transition

2区 · 医学

ArticleOA

作者: Feng, Yuan ; Sheng-Xiong, Tong ; Dan, Feng ; Shao-Jun, Li ; Jia-Yu, Tian ; Min, Li ; Shu-Li, Zhang ; Xiang-Zhi, Fang ; Han, Hu

Abstract:

Background:

Pulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis has been developed. NecroX-5 has been reported to possess anti-inflammatory, anti-oxidative and anti-tumor activities. In the present study, we aimed to determine whether NecroX-5 exhibits antifibrotic property in bleomycin (BLM)-induced pulmonary fibrosis.

Results:

We found that pre-treatment with NecroX-5 alleviated inflammatory response, reduced oxidative stress, inhibited epithelial–mesenchymal transition (EMT), and ameliorated pulmonary fibrosis in vivo and in vitro. Our data further indicated that NecroX-5 substantially reduced activation of NLRP3 inflammasome and TGF-β1/Smad2/3 signaling in vivo and in vitro. Additionally, NLRP3 overexpression significantly reversed the protective effects of NecroX-5 in lung epithelial cells exposed to BLM.

Conclusions:

Overall, our results demonstrate the potent antifibrotic properties of NecroX-5 and its therapeutic potential for pulmonary fibrosis.

100 项与 NecroX-5 相关的药物交易

登录后查看更多信息