Ferrostatin-1 improves BMSC survival by inhibiting ferroptosis

Xie, Qiumin; Sun, Yanting; Xu, Hao; Chen, Tangtian; Han, Xianpei; Liu, Huiwen; Wang, Rui; Tan, Bin; Yi, Qiu; Tian, Jie; Zhu, Jing

doi:10.1016/j.abb.2023.109535

Cited by 12 publications

(10 citation statements)

References 27 publications

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“…45 LPS negatively regulates AMPK, whereas Fer-1 induces AMPK phosphorylation. 46 Therefore, the micelles may boost IL-10 release via activating AMPK. Altogether, ferroptosis inhibition by radical trapping micelles could essentially mitigate inflammation at the cellular level (Figure 3g).…”

Section: Resultsmentioning

confidence: 99%

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Attenuating Uncontrolled Inflammation by Radical Trapping Chiral Polymer Micelles

Wang

Luo

et al. 2023

ACS Nano

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As a clinical unmet need, uncontrolled inflammation is characterized by the crosstalk between oxidative stress and an inflammatory response. Ferroptotic cell death plays an essential role in uncontrolled inflammation. Hence ferroptosis inhibition is capable of managing hyper-inflammation, but the small molecular inhibitors show poor residence in cell membranes. The plasma membrane is the major site of lipid peroxidation that is the key event of ferroptosis. To address such a challenge, chiral radical trapping polymers were engineered by mimicking the structure of the cell membrane with imbedded helical proteins. The polymers were tailored to show an α-helix conformation that enabled increased hydrophobicity, prolonged membrane retention, and enhanced lipid radical trapping. The chiral polymers are amphiphilic, and the self-assembled micelles exhibited an extended blood circulation. At the lipopolysaccharide-induced macrophage and mice models, chiral polymer micelles effectively suppressed ferroptosis and repressed inflammatory cytokines. The current work provides an innovative means for attenuating uncontrolled inflammation by anti-ferroptotic polymer micelles.

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Section: Resultsmentioning

confidence: 99%

“…Previous work showed that the phosphorylation of AMP-activated protein kinase (AMPK) could trigger IL-10 production . LPS negatively regulates AMPK, whereas Fer-1 induces AMPK phosphorylation . Therefore, the micelles may boost IL-10 release via activating AMPK.…”

Section: Resultsmentioning

confidence: 99%

Attenuating Uncontrolled Inflammation by Radical Trapping Chiral Polymer Micelles

Wang

Luo

et al. 2023

ACS Nano

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“…Moreover, ferroptosis of hUCMSCs is reduced by regulating the CSE/H 2 S pathway, which improves vascular remodeling in mice with hypoxia-induced PAH via maintaining the balance between stem cell maintenance and differentiation[ 10 ]. While genetic modification of stem cells for CSE expression is an efficient way of preconditioning the cells against ferroptosis, alternative preconditioning strategies may also be exploited[ 29 , 39 , 40 ].…”

Section: Introductionmentioning

confidence: 99%

Cellular preconditioning and mesenchymal stem cell ferroptosis

Zineldeen,

Mushtaq,

Haider

2024

World J Stem Cells

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In this editorial, we comment on the article published in the recent issue of the World Journal of Stem Cells . They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionine γ-lyase/hydrogen sulfide (H2S) pathway as a novel approach to treat vascular disorders, particularly pulmonary hypertension. Preconditioned stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh, unfavorable microenvironment of the injured tissue. They also secrete various paracrine factors against apoptosis, necrosis, and ferroptosis to enhance cell survival. Ferroptosis, a regulated form of cell death characterized by iron accumulation and oxidative stress, has been implicated in various pathologies encompassing degenerative disorders to cancer. The lipid peroxidation cascade initiates and sustains ferroptosis, generating many reactive oxygen species that attack and damage multiple cellular structures. Understanding these intertwined mechanisms provides significant insights into developing therapeutic modalities for ferroptosis-related diseases. This editorial primarily discusses stem cell preconditioning in modulating ferroptosis, focusing on the cystathionase gamma/H2S ferroptosis pathway. Ferroptosis presents a significant challenge in mesenchymal stem cell (MSC)-based therapies; hence, the emerging role of H2S/cystathionase gamma/H2S signaling in abrogating ferroptosis provides a novel option for therapeutic intervention. Further research into understanding the precise mechanisms of H2S-mediated cytoprotection against ferroptosis is warranted to enhance the therapeutic potential of MSCs in clinical settings, particularly vascular disorders.

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“…However, although hucMSCs have achieved good efficacy in clinical trials, we still face great challenges. Differences in oxygen concentration and nutritional conditions between in vivo and in vitro may subject hucMSCs to high oxidative stress after transplantation in vivo, reducing colonization and survival rates and preventing effective treatment of damaged sites [ 35 , 7 , 8 ]. Therefore, it is particularly important to explore the molecular mechanisms that cause oxidative stress in hucMSCs, find intervening targets, and genetically modify MSCs to improve therapeutic efficacy in pediatric diseases.…”

Section: Introductionmentioning

confidence: 99%

Study of the effect of keap1 on oxidative stress in human umbilical cord mesenchymal stem cells

Deng,

Chen,

Liu

et al. 2024

Mol Biol Rep

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Background HucMSCs had shown promising efficacy in treating childhood diseases, but oxidative stress induced by the poor microenvironment at the site of damage resulted in low cell survival after transplantation, thus preventing the cells from maximizing therapeutic efficacy. Therefore, this study aimed to investigate the role and mechanism of keap1 in oxidative stress injury of human umbilical cord mesenchymal stem cells (hucMSCs), and to provide theoretical support for improving the efficacy of stem cell therapy. Methods The hucMSCs were treated with hypoxic low-sugar-free serum (GSDH) to mimic the damaged site microenvironment after implantation. Adenoviral overexpression of keap1 gene of hucMSCs was performed in vitro, and cell proliferation ability was detected by CCK8 assay, crystal violet staining assay, and cell cycle assay. Cellular redox level was assessed by Amplex Red, MDA, and GSH/GSSG kit. Mitochondrial morphology was evaluated by mitotracker Red staining. ATP production was estimated by ATP detection kit. The mRNA and protein expression levels were tested by western blotting and RT-qPCR. Results GSDH treatment substantially upregulated keap1 expression. Subsequently, we found that overexpression of keap1 notably inhibited cell proliferation and caused cells to stagnate in G1 phase. At the same time, overexpression of keap1 induced the production of large amounts of H2O2 and the accumulation of MDA, but suppressed the GSH/GSSG ratio and the expression of antioxidant proteins NQO1 and SOD1, which caused oxidative stress damage. Overexpression of keap1 induced cells to produce a large number of dysfunctional mitochondria resulting in reduced ATP production. Moreover, Overexpression of keap1 significantly decreased the IKKβ protein level, while upregulating IkB mRNA levels and downregulating P50 mRNA levels. Conclusions Overexpression of keap1 may induce oxidative stress injury in hucMSCs by down-regulating IKKβ expression and inhibiting NF-κB pathway activation. This implies the importance of keap1 in hucMSCs and it may be a potential gene for genetic modification of hucMSCs.

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Ferrostatin-1 improves BMSC survival by inhibiting ferroptosis

Cited by 12 publications

References 27 publications

Attenuating Uncontrolled Inflammation by Radical Trapping Chiral Polymer Micelles

Attenuating Uncontrolled Inflammation by Radical Trapping Chiral Polymer Micelles

Cellular preconditioning and mesenchymal stem cell ferroptosis

Study of the effect of keap1 on oxidative stress in human umbilical cord mesenchymal stem cells

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