ArticleJournal of translational medicine2023
Glutathione Peroxidase 3 induced mitochondria-mediated apoptosis via AMPK /ERK1/2 pathway and resisted autophagy-related ferroptosis via AMPK/mTOR pathway in hyperplastic prostate.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 55 citations in OpenAlex.
- Metabolic Mechanisms of Hexavalent Chromium-Induced Splenic Immune Injury via Oxidative Stress and Ferroptosis Pathways in New Zealand Rabbits.Metabolites · 2026Article
- Glutathione peroxidase 3 preserves hepatocyte mitochondrial quality control to enhance macrophage pro-regenerative phenotype during liver regeneration.Clinical and translational medicine · 2026Article
- MMP7-Triggered mitophagy by regulating parkin-mediated ubiquitination of VDAC1 confers anoikis resistance in the epithelium of hyperplastic prostate.Cell death & disease · 2026Article
- Astrocytic FABP5 drives non-cell-autonomous oligodendrocyte injury in multiple system atrophy by promoting TNF signaling and ferroptotic stress.Redox biology · 2026Article
- Intestinal Epithelial Cell Ferroptosis in Ulcerative Colitis: Pathogenesis, Signaling Networks, and Therapeutic Implications.Current medical science · 2026Review
- Development of an AAPH-Induced Oxidative Stress Model in Bovine Mammary Epithelial Cells and Investigation of Its Molecular Mechanisms.Antioxidants (Basel, Switzerland) · 2026Article
- Identification and validation of genes associated with mitochondria in cerebral infarction and benign prostatic hyperplasia.Frontiers in medicine · 2026Article
- Topical WIN 55 212-2 Confers Long-Term Intraocular Pressure-Independent Neuroprotection in the DBA/2J Mouse Model of Glaucoma.Ophthalmology science · 2026Article
- The role of programmed cell death in chronic obstructive pulmonary disease: from pathogenesis to treatment.Frontiers in immunology · 2026Review
- Ferroptosis-related Biotargets and Network Mechanisms of Maslinic Acid Against Myocardial Ischemia-reperfusion Injury: An Integrated Bioinformatic and Experimental Approach.Combinatorial chemistry & high throughput screening · 2026Article
- Observational
- Pleiotrophin modulates cell proliferation, prostate smooth muscle contraction and fibrosis in hyperplastic prostate.Journal of translational medicine · 2025Article
- The role of the Wnt/BDNF pathway in maternal SCH-induced autism-like phenotypes in offspring rats: behavioral and molecular mechanisms.Translational psychiatry · 2025Article
- Development and validation of a lipid metabolism-related prognostic model for gastric adenocarcinoma.Translational cancer research · 2025Article
- The role of phosphatidylinositol (18:1_18:1) in benign prostatic hyperplasia: an integrated study of Mendelian randomization and network pharmacology.World journal of urology · 2025Article
- From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).International journal of oncology · 2025Review
- Crosstalk between mitochondrial dysfunction and benign prostatic hyperplasia: unraveling the intrinsic mechanisms.The Canadian journal of urology · 2025Review
- Dissecting regulated cell death states and transformation mechanisms in the evolutionary trajectory of 30 cancers.iScience · 2025Article
- Hydroxycitric acid inhibits ferroptosis and ameliorates benign prostatic hyperplasia by upregulating the Nrf2/GPX4 pathway.World journal of urology · 2025Article
- Heat Shock Protein Family A Member 1A Attenuates Apoptosis and Oxidative Stress via ERK/JNK Pathway in Hyperplastic Prostate.MedComm · 2025Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBenign prostatic hyperplasia (BPH) is a common disease in elderly men, mainly resulted from an imbalance between cell proliferation and death. Glutathione peroxidase 3 (GPX3) was one of the differentially expressed genes in BPH identified by transcriptome sequencing of 5 hyperplastic and 3 normal prostate specimens, which had not been elucidated in the prostate. This study aimed to ascertain the mechanism of GPX3 involved in cell proliferation, apoptosis, autophagy and ferroptosis in BPH.
methodsHuman prostate tissues, GPX3 silencing and overexpression prostate cell (BPH-1 and WPMY-1) models and testosterone-induced rat BPH (T-BPH) model were utilized. The qRT-PCR, CCK8 assay, flow cytometry, Western blotting, immunofluorescence, hematoxylin and eosin, masson's trichrome, immunohistochemical staining and transmission electron microscopy analysis were performed during in vivo and in vitro experiments.
resultsOur study indicated that GPX3 was localized both in the stroma and epithelium of prostate, and down-regulated in BPH samples. Overexpression of GPX3 inhibited AMPK and activated ERK1/2 pathway, thereby inducing mitochondria-dependent apoptosis and G0/G1 phase arrest, which could be significantly reversed by MEK1/2 inhibitor U0126 preconditioning. Moreover, overexpression of GPX3 further exerted anti-autophagy by inhibiting AMPK/m-TOR and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4, mitochondrial GPX4 and cytoplasmic GPX4) to antagonize autophagy-related ferroptosis. Consistently, GPX3 deficiency generated opposite changes in both cell lines. Finally, T-BPH rat model was treated with GPX3 indirect agonist troglitazone (TRO) or GPX4 inhibitor RAS-selective lethal 3 (RSL3) or TRO plus RSL3. These treatments produced significant atrophy of the prostate and related molecular changes were similar to our in vitro observations.
conclusionsOur novel data manifested that GPX3, which was capable of inducing apoptosis via AMPK/ERK1/2 pathway and antagonizing autophagy-related ferroptosis through AMPK/m-TOR signalling, was a promising therapeutic target for BPH in the future.
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