ArticleJournal of the American Heart Association2016
HECT-Type Ubiquitin E3 Ligase ITCH Interacts With Thioredoxin-Interacting Protein and Ameliorates Reactive Oxygen Species-Induced Cardiotoxicity.
Article in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- ITCH-Mediated Ubiquitination and Degradation of THBS1: A Key Mechanism for Enhancing Mitochondrial Biogenesis and Alleviating Mouse Skeletal Muscle Atrophy.Acta physiologica (Oxford, England) · 2026Article
- Mutations in the Txnip PPXY motifs protect against myocardial infarction despite enhanced protein stability.American journal of physiology. Heart and circulatory physiology · 2026Article
- The E3 ubiquitin ligase Itch plays an essential role in kidney fibrosis by inhibiting Dvl2/GSK3β/β-catenin signaling pathway.Cell death and differentiation · 2026Article
- Taohong Siwu Decoction Regulates MSC-Mediated H-Type Angiogenesis to Accelerate Bone Fracture Healing Through VHL/HIF-1α Ubiquitination.Mediators of inflammation · 2026Article
- Review
- Ubiquitin E3 Ligases and p53 in Doxorubicin-Induced Cardiotoxicity.International journal of molecular sciences · 2025Review
- Oxidative stress triggers Itch-mediated TXNIP degradation and NF-κB activation promoting chronic obstructive pulmonary disease.Respiratory research · 2025Article
- Exosomal transfer of pro-pyroptotic miR-216a-5p exacerbates anthracycline cardiotoxicity through breast cancer-heart pathological crosstalk.Signal transduction and targeted therapy · 2025Article
- Cardiotoxicity of Chemotherapy: A Multi-OMIC Perspective.Journal of xenobiotics · 2025Review
- Diacylglycerol Kinase ζ Attenuates Doxorubicin-Induced Cardiotoxicity Through p53 Degradation.Journal of the American Heart Association · 2025Article
- Novel molecular mechanisms of doxorubicin cardiotoxicity: latest leading-edge advances and clinical implications.Molecular and cellular biochemistry · 2024Review
- Molecular Regulation of Transforming Growth Factor-β1-induced Thioredoxin-interacting Protein Ubiquitination and Proteasomal Degradation in Lung Fibroblasts: Implication in Pulmonary Fibrosis.Journal of respiratory biology and translational medicine · 2024Article
- The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control.British journal of cancer · 2023Review
- p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act.Nutrients · 2023Review
- Regulation of MAPK Signaling Pathways by the Large HERC Ubiquitin Ligases.International journal of molecular sciences · 2023Review
- A novel NEDD4L-TXNIP-CHOP axis in the pathogenesis of nonalcoholic steatohepatitis.Theranostics · 2023Article
- Cardiac-specific ITCH overexpression ameliorates septic cardiomyopathyJournal of molecular and cellular cardiology plus · 2022Article
- ITCH deficiency clinical phenotype expansion and mitochondrial dysfunction.Molecular genetics and metabolism reports · 2022Article
- ITCH puts the brakes on septic cardiomyopathy.Journal of molecular and cellular cardiology plus · 2022Article
- Siah2-GRP78 interaction regulates ROS and provides a proliferative advantage to Helicobacter pylori-infected gastric epithelial cancer cells.Cellular and molecular life sciences : CMLS · 2022Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe homologous to the E6-AP carboxyl terminus (HECT)-type ubiquitin E3 ligase ITCH is an enzyme that plays a pivotal role in posttranslational modification by ubiquitin proteasomal protein degradation. Thioredoxin-interacting protein (TXNIP) is a negative regulator of the thioredoxin system and an endogenous reactive oxygen species scavenger. In the present study, we focused on the functional role of ubiquitin E3 ligase ITCH and its interaction with TXNIP to elucidate the mechanism of cardiotoxicity induced by reactive oxygen species, such as doxorubicin and hydrogen peroxide. METHODS AND
resultsProtein interaction between TXNIP and ITCH in cardiomyocyte was confirmed by immunoprecipitation assays. Overexpression of ITCH increased proteasomal TXNIP degradation and augmented thioredoxin activity, leading to inhibition of reactive oxygen species generation, p38 MAPK, p53, and subsequent intrinsic pathway cardiomyocyte apoptosis in reactive oxygen species-induced cardiotoxicity. Conversely, knockdown of ITCH using small interfering RNA inhibited TXNIP degradation and resulted in a subsequent increase in cardiomyocyte apoptosis. Next, we generated a transgenic mouse with cardiac-specific overexpression of ITCH, called the ITCH-Tg mouse. The expression level of TXNIP in the myocardium in ITCH-Tg mice was significantly lower than WT littermates. In ITCH-Tg mice, cardiac dysfunction and remodeling were restored compared with WT littermates after doxorubicin injection and myocardial infarction surgery. Kaplan-Meier analysis revealed that ITCH-Tg mice had a higher survival rate than WT littermates after doxorubicin injection and myocardial infarction surgery.
conclusionWe demonstrated, for the first time, that ITCH targets TXNIP for ubiquitin-proteasome degradation in cardiomyocytes and ameliorates reactive oxygen species-induced cardiotoxicity through the thioredoxin system.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.