ArticleThe Journal of clinical investigation2002
Benzodiazepine-induced superoxide signals B cell apoptosis: mechanistic insight and potential therapeutic utility.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Pharmacological restoration of mitochondrial permeability transition pore flickering by high-content drug repurposing.Pharmacological research · 2026Article
- Chemically gated artificial nanochannels for programmable subcellular signal modulated transport regulation.Nature communications · 2025Article
- Differential response of patient-derived primary glioblastoma cells to metabolic and adhesion inhibitors.Clinical and experimental medicine · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- B cell metabolism in autoimmune diseases: signaling pathways and interventions.Frontiers in immunology · 2023Review
- Modulation and Pharmacology of the Mitochondrial Permeability Transition: A Journey from F-ATP Synthase to ANT.Molecules (Basel, Switzerland) · 2021Review
- Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?Journal of medicinal chemistry · 2020Review
- Impaired flickering of the permeability transition pore causes SPG7 spastic paraplegia.EBioMedicine · 2020Article
- T cell metabolism: new insights in systemic lupus erythematosus pathogenesis and therapy.Nature reviews. Rheumatology · 2020Review
- OSCP subunit of mitochondrial ATP synthase: role in regulation of enzyme function and of its transition to a pore.British journal of pharmacology · 2019Review
- Donor and host B7-H4 expression negatively regulates acute graft-versus-host disease lethality.JCI insight · 2019Article
- Purified F-ATP synthase forms a CaNature communications · 2019Article
- Targeting metabolism to regulate immune responses in autoimmunity and cancer.Nature reviews. Drug discovery · 2019Review
- Changes in Nutritional Status Impact Immune Cell Metabolism and Function.Frontiers in immunology · 2018Review
- Visualizing Mitochondrial FFrontiers in physiology · 2018Review
- A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase.Current medicinal chemistry · 2017Review
- Design, synthesis and evaluation of antitumor acylated monoaminopyrroloquinazolines.Bioorganic & medicinal chemistry letters · 2017Article
- Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality.The Journal of clinical investigation · 2016Article
- The Mitochondrial Permeability Transition Pore: Channel Formation by F-ATP Synthase, Integration in Signal Transduction, and Role in Pathophysiology.Physiological reviews · 2015Review
- Ca(2+) and caspases are involved in hydroxyl radical-induced apoptosis in erythrocytes of Jian carp (Cyprinus carpio var. Jian).Fish physiology and biochemistry · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The properties of a proapoptotic 1,4-benzodiazepine, Bz-423, identified through combinatorial chemistry and phenotype screening are described. Bz-423 rapidly generated superoxide (O(2)(-)) in transformed Ramos B cells. This O(2)(-) response originated from mitochondria prior to mitochondrial transmembrane gradient collapse and opening of the permeability transition pore. Bz-423-induced O(2)(-) functioned as an upstream signal that initiated an apoptotic program characterized by cytochrome c release, mitochondrial depolarization, and caspase activation. Pretreatment of cells with agents that either block the formation of Bz-423-induced O(2)(-) or scavenge free radicals attenuated the death cascade, which demonstrated that cell killing by Bz-423 depends on O(2)(-). Parallels between Ramos cells and germinal center B cells prompted experiments to determine whether Bz-423 had therapeutic activity in vivo. This possibility was tested using the (NZB x NZW)F(1) murine model of lupus, in which the pathologically enhanced survival and expansion of germinal center B cells mediate disease. Administration of Bz-423 for 12 weeks specifically controlled germinal center hyperplasia and reduced the histological evidence of glomerulonephritis. Collectively, these studies define a new structure-function relationship for benzodiazepines and point to a new target and mechanism that could be of value for developing improved drugs to manage systemic lupus erythematosus and related disorders.
Indexed as
Identifiers
What OpenQuestion holds
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.