Melatonin attenuates spinal cord injury by regulating ferroptosis through the Nrf2/HO-1/GPX4 pathway DOI Creative Commons

Zhengxi Yu,

Dingwei Wu, Tengbin Shi

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Abstract Spinal cord injury (SCI) is one of the most devastating and catastrophic types injury, with high rates mortality disability. Ferroptosis has become target many major incurable human diseases. By inhibiting ferroptosis, melatonin (MT) can reduce damage in various organs, but protective effect MT on SCI not been reported yet. The modified Ellen's method was used to establish an rat model. spinal neurons recovery motor function were observed. In vitro experiments, oxygen-glucose deprivation/reoxygenation (OGD/R) model established by using mouse hippocampal neuron (HT22) cells simulate ischemia-reperfusion injury. A ferroptosis directly induced Erastin also used. nuclear factor erythroid 2-related 2 (Nrf2) inhibitor ML 385 further detect mechanism through which inhibits protects neuronal cells. Our study demonstrates that rats, promote behavior injured tissue after SCI. Under electron microscope, inhibited rescued damaged mitochondria, partially restored mitochondrial structure. ML385, Nrf2 inhibitor, reversed effects MT. Overall, may alleviate early activating Nrf2/heme oxygenase-1(HO-1)/glutathione peroxidase 4 (GPX 4) pathway.

Язык: Английский

CAV1 promotes epithelial-to-mesenchymal transition (EMT) and chronic renal allograft interstitial fibrosis by activating the ferroptosis pathway DOI Creative Commons

Qianguang Han,

Bing Ni,

Wei Bao

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 12, 2025

Background Chronic allograft dysfunction (CAD) stands as a critical factor that limits the long-term viability of transplanted kidneys. Ferroptosis is an iron-dependent form programmed cell death increasingly linked to chronic fibrosis. However, mechanism by which ferroptosis contributes onset and progression CAD remains unclear. Methods This study analyzed transcriptome data from renal transplant biopsy samples in Gene Expression Omnibus (GEO), through clinical samples, animal models, experiments, this investigated Caveolin-1 (CAV1) promotes regulation pathway. Results The elevated levels CAV1 were found positively correlate with incidence. Clinical model validation confirmed heightened expression CAD. In vitro experiments demonstrated can directly promote interstitial fibrosis regulating tubular epithelial cells; additionally, it epithelial-to-mesenchymal transition (EMT) secreting Interleukin- 6 (IL-6), thereby further contributing Conclusion plays role development promoting EMT Adjusting altering abundance may become important method for prevention treatment future.

Язык: Английский

Процитировано

0
Perfluorooctane sulfonate mediates GSH degradation leading to oral keratinocytes ferroptosis and mucositis through activation of the ER stress-ATF4-CHAC1 axis DOI Creative Commons
Ningning Yang, Kun Jia, Kazuoki Dai

и другие.

Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 292, С. 117964 - 117964

Опубликована: Март 1, 2025

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that induces inflammatory response and oxidative stress in oral mucosa. Ferroptosis, form of cell death characterized by iron-dependent lipid peroxidation (the degradation lipids), was believed to play crucial role pathogenesis mucositis; however, the involvement PFOS-induced ferroptosis remained unclear. Our findings demonstrated PFOS inhibited proliferation induced pro-apoptotic effects cells, with most pronounced observed human keratinocytes (HOK). significantly increased reactive oxygen species (ROS) peroxidation, depleted glutathione (GSH) HOK cells. Notably, decreased peroxidase 4 (GPX4) expression elevated Fe2 + levels, suggesting potential induction ferroptosis. Ferroptosis inhibitors mitigated GSH depletion, subsequently enhancing viability. Mechanistically, endoplasmic reticulum (ER) contributed nuclear translocation (from cytoplasm into nucleus) activating transcription factor (ATF4) up-regulated its downstream target gene Chac1. Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1) catalyzed conversion cysteinylglycine 5-oxoproline, resulting depletion-a critical Knocking down CHAC1 attenuated Tauroursodeoxycholic acid (TUDCA), classical ER inhibitor, mucositis inhibiting ATF4/CHAC1 pathway activation. These elucidated toxicological mechanisms proposed therapeutic strategies counteract exposure mucositis.

Язык: Английский

Процитировано

0
Cutting edge: ferroptosis in metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis and therapy DOI

Amr Ali Mohamed Abdelgawwad El-Sehrawy,

Teeba Ammar Rashid,

Muhammad Ikram Ullah

и другие.

Functional & Integrative Genomics, Год журнала: 2025, Номер 25(1)

Опубликована: Март 25, 2025

Язык: Английский

Процитировано

0
MAM kinases: physiological roles, related diseases, and therapeutic perspectives—a systematic review DOI Creative Commons

Avinash Mohan,

Priti Talwar

Cellular & Molecular Biology Letters, Год журнала: 2025, Номер 30(1)

Опубликована: Март 28, 2025

Abstract Mitochondria-associated membranes (MAMs) are tethering regions amid the of endoplasmic reticulum (ER) and mitochondria. They a lipid raft-like structure occupied by various proteins that facilitates signal transduction between two organelles. The MAM proteome participates in cellular functions such as calcium (Ca 2+ ) homeostasis, synthesis, ER stress, inflammation, autophagy, mitophagy, apoptosis. human kinome is superfamily homologous consisting 538 kinases. MAM-associated kinases participate aforementioned act cell fate executors. Studies have proved dysregulated kinase interactions an etiology for diseases including cancer, diabetes mellitus, neurodegenerative diseases, cardiovascular (CVDs), obesity. Several small inhibitory molecules been well explored promising drug candidates clinical trials with accelerating impact field precision medicine. This review narrates physiological actions, pathophysiology, therapeutic potential recent updates field. Graphical

Язык: Английский

Процитировано

0
Melatonin attenuates spinal cord injury by regulating ferroptosis through the Nrf2/HO-1/GPX4 pathway DOI Creative Commons

Zhengxi Yu,

Dingwei Wu, Tengbin Shi

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Abstract Spinal cord injury (SCI) is one of the most devastating and catastrophic types injury, with high rates mortality disability. Ferroptosis has become target many major incurable human diseases. By inhibiting ferroptosis, melatonin (MT) can reduce damage in various organs, but protective effect MT on SCI not been reported yet. The modified Ellen's method was used to establish an rat model. spinal neurons recovery motor function were observed. In vitro experiments, oxygen-glucose deprivation/reoxygenation (OGD/R) model established by using mouse hippocampal neuron (HT22) cells simulate ischemia-reperfusion injury. A ferroptosis directly induced Erastin also used. nuclear factor erythroid 2-related 2 (Nrf2) inhibitor ML 385 further detect mechanism through which inhibits protects neuronal cells. Our study demonstrates that rats, promote behavior injured tissue after SCI. Under electron microscope, inhibited rescued damaged mitochondria, partially restored mitochondrial structure. ML385, Nrf2 inhibitor, reversed effects MT. Overall, may alleviate early activating Nrf2/heme oxygenase-1(HO-1)/glutathione peroxidase 4 (GPX 4) pathway.

Язык: Английский

Процитировано

0