Mesenchymal Stem Cells Prevent SLC39A14‐Dependent Hepatocyte Ferroptosis through Exosomal miR‐16‐5p in Liver Graft DOI Creative Commons

Zhizhao Deng,

Weiqi Zeng,

Yingxin Gao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Ischemia‐reperfusion injury (IRI) is the leading cause of hepatic graft dysfunction, resulting from hepatocyte damage. Nevertheless, given few specialized therapeutics available in IRI, additional mechanistic insights into damage are required. Here, protein solute carrier family 39 member 14 (SLC39A14) identified as a pro‐ferroptosis target hepatocytes human liver allografts through single‐cell RNA sequencing analysis. SLC39A14 knockdown significantly mitigated IRI by preventing ferroptosis vivo and vitro. Mechanistically, inhibition suppressed non‐transferrin‐bound iron (NTBI) uptake hepatocytes, thereby reducing overload cell ferroptosis. Moreover, bone marrow‐derived mesenchymal stem cells (hBMSCs) found to exhibit notable therapeutic effect on downregulating expression. Exosomes derived hBMSCs delivered abundant miR‐16‐5p which post‐transcriptionally expression reduced induced IRI. In conclusion, triggers mediating NTBI inducing hBMSC‐based therapy promising reverse this progression

Language: Английский

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases DOI Creative Commons
Yumin Wang, Jing Hu, Shuang Wu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

Citations

72
The mechanism of ferroptosis and its related diseases DOI Creative Commons
Shijian Feng, Dan Tang, Yichang Wang

et al.

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

Citations

62
GPX4, ferroptosis, and diseases DOI Open Access

Wangzheqi Zhang,

Yang Liu,

Liao Yan

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116512 - 116512

Published: April 3, 2024

GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.

Language: Английский

Citations

54
FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC DOI Creative Commons
Rong Li, Xijing Yan, Cuicui Xiao

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 4, 2024

Abstract Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older exhibit increased ferroptosis during HIRI. Inhibiting significantly attenuates HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated livers, especially Overexpressing FTO improves phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) transferrin receptor protein 1 (TFRC), two key positive contributors ferroptosis, targets. For ameliorative effect, requires the inhibition of Acsl4 Tfrc mRNA stability a m6A-dependent manner. Furthermore, nicotinamide mononucleotide can upregulate demethylase activity, suppressing decreasing Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway contributes pathogenesis HIRI, providing insight into clinical translation strategies related activity improve graft function after donor

Language: Английский

Citations

17
Ferroptosis Regulated by Hypoxia in Cells DOI Creative Commons
Xiangnan Zheng,

Yuqiong Liang,

Cen Zhang

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(7), P. 1050 - 1050

Published: March 30, 2023

Ferroptosis is an oxidative damage-related, iron-dependent regulated cell death with intracellular lipid peroxide accumulation, which associated many physiological and pathological processes. It exhibits unique features that are morphologically, biochemically, immunologically distinct from other forms. by iron metabolism, anti-oxidant defense systems, as well various signal pathways. Hypoxia, found in a group of conditions, can affect multiple cellular functions activation the hypoxia-inducible factor (HIF) signaling mechanisms. Emerging evidence demonstrated hypoxia regulates ferroptosis certain types conditions. In this review, we summarize basic mechanisms regulations hypoxia, regulation may contribute to numerous diseases therapies.

Language: Английский

Citations

33
The ubiquitin–proteasome system links NADPH metabolism to ferroptosis DOI
Jihye Yang, Yoontae Lee, Cheol‐Sang Hwang

et al.

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 33(12), P. 1088 - 1103

Published: Aug. 7, 2023

Language: Английский

Citations

24
Ferroptosis in organ ischemia–reperfusion injuries: recent advancements and strategies DOI

Xiaoyu Luan,

Peng Chen, Longyu Miao

et al.

Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: March 31, 2024

Language: Английский

Citations

11
Ferroptosis in liver cancer: a key role of post-translational modifications DOI Creative Commons
Ying Xu,

Zhiyao Xing,

Ruaa Abdalla Ibrahim Suliman

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 8, 2024

Ferroptosis is an emerging form of regulated cell death in oxidative stress- and iron-dependent manner, primarily induced by the over-production reactive oxygen species (ROS). Manipulation ferroptosis has been considered a promising therapeutic approach to inhibit liver tumor growth. Nevertheless, development resistance cancer poses significant challenge treatment. Post-translational modifications (PTMs) are crucial enzymatic catalytic reactions that covalently regulate protein conformation, stability cellular activities. Additionally, PTMs play pivotal roles various biological processes divergent programmed death, including ferroptosis. Importantly, key regulators involved have identified as potential targets for therapy. function two proteins, SLC7A11, GPX4 extensively investigated recent years. This review will summarize ferroptosis-related proteins hepatocellular carcinoma (HCC)

Language: Английский

Citations

6
Genetic and pharmacological targeting of XBP1 alleviates hepatic ischemia reperfusion injury by enhancing FoxO1-dependent mitophagy DOI

Baicheng Kuang,

Mengqin Wang, Hao Yan

et al.

Translational research, Journal Year: 2024, Volume and Issue: 272, P. 162 - 176

Published: March 15, 2024

Language: Английский

Citations

5
Ferroptosis-based advanced therapies as treatment approaches for metabolic and cardiovascular diseases DOI Creative Commons
Francesca Maremonti, Wulf Tonnus, Shubhangi Gavali

et al.

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: 31(9), P. 1104 - 1112

Published: July 27, 2024

Ferroptosis has attracted attention throughout the last decade because of its tremendous clinical importance. Here, we review rapidly growing body literature on how inhibition ferroptosis may be harnessed for treatment common diseases, and focus metabolic cardiovascular unmet medical needs. We introduce four classes preclinically established inhibitors (ferrostatins) such as iron chelators, radical trapping agents that function in cytoplasmic compartment, lipophilic antioxidants ninjurin-1 (NINJ1) specific monoclonal antibodies. In contrast to inducers cause serious untoward effects acute kidney tubular necrosis, side effect profile ferrostatins appears limited. also consider a potential itself when several advanced therapies harnessing small-interfering RNA (siRNA)-based approaches are tested. Importantly, trial design is impeded by lack an appropriate biomarker detection serum samples or tissue biopsies. However, discuss favorable scenarios suited anti-ferroptosis trials test first-in-class compounds. conclude targeting exhibits outstanding options but have only begun translate this knowledge into clinically relevant applications.

Language: Английский

Citations

5