ArticleCell biochemistry and biophysics2013
Homocysteine-induced apoptosis in endothelial cells coincides with nuclear NOX2 and peri-nuclear NOX4 activity.
Article in Cell biochemistry and biophysics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 72 citations in OpenAlex.
- Hydrogen peroxide sensing and signaling in physiology and disease: implications for therapy.Signal transduction and targeted therapy · 2026Review
- Modulation of mitochondrial voltage dependent anion channel: studies on bilayer electrophysiology.Frontiers in physiology · 2025Review
- Review
- Clinical relevance of critical plasma homocysteine levels in predicting rupture risk for small and medium-sized intracranial aneurysms.Scientific reports · 2024Article
- Effects of Aerobic Treadmill Training on Oxidative Stress Parameters, Metabolic Enzymes, and Histomorphometric Changes in Colon of Rats with Experimentally Induced Hyperhomocysteinemia.International journal of molecular sciences · 2024Article
- Beyond Glucose: The Dual Assault of Oxidative and ER Stress in Diabetic Disorders.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2023Review
- Clozapine suppresses NADPH oxidase activation, counteracts cytosolic HRedox biology · 2023Article
- Epigenetic Regulation by microRNAs in Hyperhomocysteinemia-Accelerated Atherosclerosis.International journal of molecular sciences · 2022Review
- Signaling Role of NADPH Oxidases in ROS-Dependent Host Cell Death Induced by Pathogenic Entamoeba histolytica.The Korean journal of parasitology · 2022Review
- Elevated homocysteine level as an indicator for chronic kidney disease in community-dwelling middle-aged and elderly populations in Taiwan: A community-based cross-sectional study.Frontiers in medicine · 2022Article
- Current Status of Endoplasmic Reticulum Stress in Type II Diabetes.Molecules (Basel, Switzerland) · 2021Review
- The Effects of Medicinal Plants and Bioactive Natural Compounds on Homocysteine.Molecules (Basel, Switzerland) · 2021Review
- The Contribution of Homocysteine Metabolism Disruption to Endothelial Dysfunction: State-of-the-Art.International journal of molecular sciences · 2019Review
- Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic reticulum redox homeostasis.Redox biology · 2019Article
- Tetrahydrocurcumin ameliorates homocysteine-mediated mitochondrial remodeling in brain endothelial cells.Journal of cellular physiology · 2018Article
- Genome-wide association study of homocysteine in African Americans from the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Coronary Artery Risk in Young Adults study.Journal of human genetics · 2018Article
- Taurine Attenuates Calpain-2 Induction and a Series of Cell Damage via Suppression of NOX-Derived ROS in ARPE-19 Cells.Oxidative medicine and cellular longevity · 2018Article
- Toll-like receptor 4 mediates vascular remodeling in hyperhomocysteinemia.Molecular and cellular biochemistry · 2017Review
- Upregulation of DAPK contributes to homocysteine-induced endothelial apoptosis via the modulation of Bcl2/Bax and activation of caspase 3.Molecular medicine reports · 2016Article
- Toll-like receptor 4 mutation suppresses hyperhomocysteinemia-induced hypertension.American journal of physiology. Cell physiology · 2016Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptosis of endothelial cells related to homocysteine (Hcy) has been reported in several studies. In this study, we evaluated whether reactive oxygen species (ROS)-producing signaling pathways contribute to Hcy-induced apoptosis induction, with specific emphasis on NADPH oxidases. Human umbilical vein endothelial cells were incubated with 0.01-2.5 mM Hcy. We determined the effect of Hcy on caspase-3 activity, annexin V positivity, intracellular NOX1, NOX2, NOX4, and p47(phox) expression and localization, nuclear nitrotyrosine accumulation, and mitochondrial membrane potential (ΔΨ m). Hcy induced caspase-3 activity and apoptosis; this effect was concentration dependent and maximal after 6-h exposure to 2.5 mM Hcy. It was accompanied by a significant increase in ΔΨ m. Cysteine was inactive on these parameters excluding a reactive thiol group effect. Hcy induced an increase in cellular NOX2, p47(phox), and NOX4, but not that of NOX1. 3D digital imaging microscopy followed by image deconvolution analysis showed nuclear accumulation of NOX2 and p47(phox) in endothelial cells exposed to Hcy, but not in control cells, which coincided with accumulation of nuclear nitrotyrosine residues. Furthermore, Hcy enhanced peri-nuclear localization of NOX4 coinciding with accumulation of peri-nuclear nitrotyrosine residues, a reflection of local ROS production. p47(phox) was also increased in the peri-nuclear region. The Hcy-induced increase in caspase-3 activity was prevented by DPI and apocynin, suggesting involvement of NOX activity. The data presented in this article reveal accumulation of nuclear NOX2 and peri-nuclear NOX4 accumulation as potential source of ROS production in Hcy-induced apoptosis in endothelial cells.
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