MPV17 Prevents Myocardial Ferroptosis and Ischemic Cardiac Injury through Maintaining SLC25A10-Mediated Mitochondrial Glutathione Import DOI Open Access
Tao Xu, Guilan Chen

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10832 - 10832

Published: Oct. 9, 2024

Ferroptosis is a recently identified iron-dependent programmed cell death with lipid peroxide accumulation and condensation compaction of mitochondria. A recent study indicated that ferroptosis plays pivotal role in ischemic cardiac injury the mechanisms remain largely unknown. This demonstrates when an iron overload occurs ischemia/reperfusion tissues, which initiates myocardial ferroptosis, expression levels mitochondrial inner membrane protein MPV17 are reduced. Overexpression delivered via adenovirus significantly reduced both cardiomyocytes high I/R tissues. Mitochondrial glutathione (mtGSH), crucial for reactive oxygen species scavenging homeostasis maintenance, depleted caused by overload. mechanistic shows can increase through maintaining SLC25A10, inner-membrane transporter. The absence resulted ubiquitination-dependent degradation leading to impaired import. Moreover, we found

Language: Английский

Lycobetaine Has Therapeutic Efficacy in Lung Squamous Cell Carcinoma by Targeting USP32 to Trigger Ferroptosis DOI Creative Commons
Shangping Xing, Hua Chai, Zhenlong Chen

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(3), P. 163 - 163

Published: Feb. 27, 2025

Ubiquitin-specific protease 32 (USP32), a deubiquitylating enzyme that controls the ubiquitin process, is overexpressed in multiple cancers and serves as promising therapeutic target for cancer therapy. Drugs targeting ferroptosis have exhibited anticancer activity. Lycobetaine (LBT), natural alkaloid, holds promise against various cancers, yet its specific targets mechanisms remain unclear. In this study, we show LBT induced lung squamous cell carcinoma (LUSC) cells, accompanied by glutathione depletion accumulation of lipid peroxidation, malondialdehyde, ferrous iron. Mechanistically, drug affinity responsive stability-based mass spectrometry analysis, molecular dynamics simulations, cellular thermal shift assay confirmed USP32 potential LUSC cells. Moreover, strong interaction between nuclear factor erythroid 2-related 2 (NRF2) was found via immunoprecipitation–mass co-immunoprecipitation. addition, ubiquitination results demonstrated treatment significantly increased NRF2 degradation USP32. Importantly, overexpression effectively attenuated effects on proliferation orthotopic xenografts, administration inhibited tumor growth metastasis USP32–NRF2 signaling axis. Taken together, these data suggest exerts inhibiting USP32-mediated deubiquitination to induce may serve prospective USP32-targeting agent treatment.

Language: Английский

Citations

0
Molecular Targets of Oxidative Stress: Focus on Nuclear Factor Erythroid 2–Related Factor 2 Function in Leukemia and Other Cancers DOI Creative Commons
Syed K. Hasan,

Sundarraj Jayakumar,

E Barroso

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(10), P. 713 - 713

Published: May 14, 2025

Nuclear factor erythroid 2–related 2 (Nrf2) is a transcription that plays central role in regulating cellular responses to oxidative stress. It governs the expression of broad range genes involved antioxidant defense, detoxification, metabolism, and other cytoprotective pathways. In normal cells, transient activation Nrf2 serves as protective mechanism maintain redox homeostasis. However, persistent or aberrant cancer cells has been implicated tumor progression, metabolic reprogramming, resistance chemotherapy radiotherapy. These dual roles underscore complexity signaling its potential therapeutic target. A deeper understanding regulation both malignant contexts essential for development effective Nrf2-targeted therapies. This review provides comprehensive overview function, highlighting unique features biology, particularly adaptation drug resistance. Special attention given current knowledge Nrf2′s involvement leukemia emerging strategies modulation.

Language: Английский

Citations

0
Brusatol improves the efficacy of sorafenib in Huh7 cells via ferroptosis resistance dependent Nrf2 signaling pathway DOI

Xujin Liu,

Tianyi Liu,

Zhonghua Zhou

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 734, P. 150762 - 150762

Published: Sept. 27, 2024

Language: Английский

Citations

1
In Silico Analysis of Non-Conventional Oxidative Stress-Related Enzymes and Their Potential Relationship with Carcinogenesis DOI Creative Commons
Fábio Rodrigues Ferreira Seiva, Maria Luisa Gonçalves Agneis, Matheus Ribas de Almeida

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(11), P. 1279 - 1279

Published: Oct. 23, 2024

Carcinogenesis is driven by complex molecular events, often involving key enzymes that regulate oxidative stress (OS). While classical such as SOD, catalase, and GPx have been extensively studied, other, non-classical stress-related (OSRE) may play critical roles in cancer progression. We aimed to explore the role of OSRE involved an OS scenario assess their potential contribution carcinogenesis some most prevalent types. Through data mining bioinformatic analysis gene protein expression mutation data, we identified with altered mutations across Functional pathways EGFR, MT-ND, GST, PLCG2, PRDX6, SRC, JAK2 were investigated. Our findings reveal traditionally considered peripheral significant tumor Those contribute initiation progression, well be hallmarks, EMT invasion, proliferation, ROS production. In addition, like SRC found dual both promoting generation being modulated OS. also interact oncogenic signaling pathways, including Wnt/β-catenin JAK2/STAT3, linking them aggressiveness therapeutic resistance. Future research should focus on translating these into clinical applications, development novel inhibitors or drugs targeting enzymes.

Language: Английский

Citations

1
Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies DOI Creative Commons
Ademola C. Famurewa, Roland Eghoghosoa Akhigbe,

Mina Y. George

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

Abstract Chemotherapy (CT) is one of the flagship options for treatment cancers worldwide. It involves use cytotoxic anticancer agents to kill or inhibit proliferation cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact patient’s quality life and outcomes. While toxicity consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment other aberrant signalling leading apoptosis necroptosis, recent studies show that ferroptosis, a non-apoptotic, iron-dependent cell death pathway, also involved pathophysiology organ toxicity. provokes ferroptosis via system Xc – /GPX-4/GSH/SLC7A11 axis depletion, ferritinophagy, iron overload, lipid peroxidation upregulation ferritin-related proteins. Cisplatin (CP) doxorubicin (DOX) are common drugs indicated induce vitro vivo. Studies have explored natural preventive therapeutic strategies using ginger rhizome major bioactive compounds, 6-gingerol (6G) zingerone (ZG), combat Ginger extract, 6G ZG mitigate dysfunction toxicity, but their effects on CT-induced remain unclear. Systematic investigations are, therefore, needed unfold roles ginger, as they potential prevention This review reveals ferroptotic protective against CT-induced, toxicities.

Language: Английский

Citations

1
MPV17 Prevents Myocardial Ferroptosis and Ischemic Cardiac Injury through Maintaining SLC25A10-Mediated Mitochondrial Glutathione Import DOI Open Access
Tao Xu, Guilan Chen

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10832 - 10832

Published: Oct. 9, 2024

Ferroptosis is a recently identified iron-dependent programmed cell death with lipid peroxide accumulation and condensation compaction of mitochondria. A recent study indicated that ferroptosis plays pivotal role in ischemic cardiac injury the mechanisms remain largely unknown. This demonstrates when an iron overload occurs ischemia/reperfusion tissues, which initiates myocardial ferroptosis, expression levels mitochondrial inner membrane protein MPV17 are reduced. Overexpression delivered via adenovirus significantly reduced both cardiomyocytes high I/R tissues. Mitochondrial glutathione (mtGSH), crucial for reactive oxygen species scavenging homeostasis maintenance, depleted caused by overload. mechanistic shows can increase through maintaining SLC25A10, inner-membrane transporter. The absence resulted ubiquitination-dependent degradation leading to impaired import. Moreover, we found

Language: Английский

Citations

1