ArticleRadiation research2011
Alpha particles induce apoptosis through the sphingomyelin pathway.
Article in Radiation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Influence of Subcellular Localization on the Cytotoxicity of Targeted α-Therapy.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- Targeted alpha therapy: a comprehensive analysis of the biological effects from "local-regional-systemic" dimensions.European journal of nuclear medicine and molecular imaging · 2025Review
- The therapeutic effect of adipose-derived stem cells on soft tissue injury after radiotherapy and their value for breast reconstruction.Stem cell research & therapy · 2022Review
- Mechanisms of radiation-induced endothelium damage: Emerging models and technologies.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2021Review
- Revisiting the Radiobiology of Targeted Alpha Therapy.Frontiers in medicine · 2021Review
- Fusion of lysosomes to plasma membrane initiates radiation-induced apoptosis.The Journal of cell biology · 2020Article
- Large Field Alpha Irradiation Setup for Radiobiological Experiments.Methods and protocols · 2019Article
- Design and testing of a microcontroller that enables alpha particle irradiators to deliver complex dose rate patterns.Physics in medicine and biology · 2018Article
- Radiation-Induced Endothelial Vascular Injury: A Review of Possible Mechanisms.JACC. Basic to translational science · 2018Review
- Combining Heavy-Ion Therapy with Immunotherapy: An Update on Recent Developments.International journal of particle therapy · 2018Review
- Targeting acid sphingomyelinase with anti-angiogenic chemotherapy.Cellular signalling · 2017Article
- Physical Considerations for Understanding Responses of Biological Systems to Low Doses of Ionizing Radiation: Nucleosome Clutches Constitute a Heterogeneous Distribution of Target Volumes.Health physics · 2016Article
- Antitumor immunity induced after α irradiation.Neoplasia (New York, N.Y.) · 2014Article
- p53-independent early and late apoptosis is mediated by ceramide after exposure of tumor cells to photon or carbon ion irradiation.BMC cancer · 2013Article
- Mechanisms of resistance to high and low linear energy transfer radiation in myeloid leukemia cells.Blood · 2012Article
- Dysregulation of IRP1-mediated iron metabolism causes gamma ray-specific radioresistance in leukemia cells.PloS one · 2012Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The sphingomyelin pathway involves the enzymatic cleavage of sphingomyelin to produce ceramide, a second messenger that serves as a key mediator in the rapid apoptotic response to various cell stressors. Low-linear energy transfer (LET) γ radiation can initiate this pathway, independent of DNA damage, via the cell membrane. Whether short-ranged, high-LET α particles, which are of interest as potent environmental carcinogens, radiotherapies and potential components of dirty bombs, can act through this mechanism to signal apoptosis is unknown. Here we show that irradiation of Jurkat cells with α particles emitted by the ²²⁵Ac-DOTA-anti-CD3 IgG antibody construct results in dose-dependent apoptosis. This apoptosis was significantly reduced by pretreating cells with cholesterol-depleting nystatin, a reagent known to inhibit ceramide signaling by interfering with membrane raft coalescence and ceramide-rich platform generation. The effects of nystatin on α-particle-induced apoptosis were related to disruption of the ceramide pathway and not to microdosimetry alterations, because similar results were obtained after external irradiation of the cells with a broad beam of collimated α particles using a planar ²⁴¹Am source. External irradiation allowed for more precise control of the dosimetry and geometry of the irradiation, independent of antibody binding or cell internalization kinetics. Mechanistically consistent with these findings, Jurkat cells rapidly increased membrane concentrations of ceramide after external irradiation with an average of five α-particle traversals per cell. These data indicate that α particles can activate the sphingomyelin pathway to induce apoptosis.
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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.