Ferroptosis is mainly caused by iron-mediated peroxidation of phospholipids and has recently attracted attention due to its involvement in various diseases. At the center of it is supposedly the inability of glutathione peroxidase 4 (GPX4) to reduce excess peroxidized phospholipids (e.g., phosphatidylcholine hydroperoxide (PCOOH)) that trigger ferroptosis. However, the involvement of enzymes other than GPX4 in ferroptosis is scarcely known. To elucidate this matter, we evaluated the uptake of PCOOH in a GPX4 knockout (KO) human hepatoma cell line HepG2 generated using CRISPR-Cas9. After confirming that GPX4 expression in the KO cells was below the detection limit, we cultured both wild-type (WT) and GPX4 KO HepG2 cells in a medium containing 50 μM PCOOH for 1-8 hours. By analyzing the level of PCOOH and its reduction product (phosphatidylcholine hydroxide, PCOH) in cells using liquid chromatography-tandem mass spectrometry, we detected the cellular uptake of PCOOH. On top of this, we detected a large amount of PCOH not only in WT HepG2 but also in GPX4 KO HepG2, thus indicating the notable involvement of enzymes other than GPX4 (e.g., other GPX family, glutathione S-transferase, thioredoxin, or peroxiredoxin) in reducing PCOOH. Further corroboration of these findings hopefully leads to the development of novel methods to prevent ferroptosis-related diseases by targeting enzymes other than GPX4.
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http://dx.doi.org/10.5650/jos.ess22281 | DOI Listing |
World J Surg Oncol
December 2024
Department of Breast Surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, No.7 Weiwu Road, Zhengzhou, Henan, 450003, China.
Background: We aim to explore the impact of excessive glutathione (GSH) intake on chemotherapy sensitivity in breast cancer.
Methods: Clinicopathological data were collected from 460 breast cancer patients who underwent adjuvant chemotherapy from January 2016 to December 2019 from Zhengzhou University People's Hospital. The clinicopathological characteristics following GSH treatment were collected and compared with those in Non-GSH group after 1:2 propensity score matching (PSM).
Biol Direct
December 2024
Department of Gynaecology and Obstetrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China.
This study explores the epigenetic mechanism of MLL1 regulating trophoblast ferroptosis in preeclampsia (PE). A murine model of PE was established, and HTR-8/SVneo cells were induced by Erastin to establish an in vitro cell model. GSH, MDA, Fe, and ROS levels were measured to assess ferroptosis.
View Article and Find Full Text PDFRadiother Oncol
December 2024
Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University,Guangzhou,510000,China. Electronic address:
Purpose: Radiotherapy presents a curative approach for nasopharyngeal carcinoma (NPC); however, the cellular radiosensitivity heterogeneity limits its efficacy. Thus, investigating the specific mechanisms of radioresistance in NPC is crucial for identifying and employing effective radiosensitizing agents to enhance treatment success.
Methods And Materials: Radioresistant NPC cell lines HONE1-RR and SUNE1-RR were established.
Phytomedicine
December 2024
The Department of Hepato-biliary-pancreatic Surgery, The Institute of Hepatobiliary and Pancreatic Diseases, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, PR China; Changzhou Medical Center, Nanjing Medical University, Changzhou, PR China. Electronic address:
Background: Abnormal antioxidant capacity in cancer cells is intimately linked to tumor aggressiveness. Modulating oxidative stress status and inhibiting ferroptosis represents a novel anticancer therapeutic strategy. STAM Binding Protein Like 1 (STAMBPL1), a deubiquitinase, is implicated in various malignancies, yet its function in inhibiting ferroptosis and therapeutic potential for cholangiocarcinoma (CCA) remains unexplored.
View Article and Find Full Text PDFJ Am Heart Assoc
December 2024
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology Wuhan University Wuhan China.
Background: Ferroptosis is a programmed cell death caused by iron-dependent accumulation and cellular lipid peroxides, which is different from apoptosis and pyroptosis. This study investigated the possible effect of ferroptotic response in the pathogenesis of infantile hemangioma (IH).
Methods And Results: The staining level of 4-hydroxynonenal (4-HNE), the marker of ferroptotic cells, was significantly increased in the involutive IH samples compared with the proliferative samples (9 proliferative versus 12 involutive lesions, =0.
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