ArticleCardiovascular research2015
Inhibition of NAADP signalling on reperfusion protects the heart by preventing lethal calcium oscillations via two-pore channel 1 and opening of the mitochondrial permeability transition pore.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019Pooled it
- Age-related changes in lysosomal abundance in mouse hearts assessed by Lysotracker fluorescence imaging and autophagy gene expression analysis.The international journal of cardiovascular imaging · 2026Article
- Allosteric switching of CaThe EMBO journal · 2026Article
- Activation of TPC2 amplifies lysosome-mitochondria calcium transfer to regulate energetic stress responses.bioRxiv : the preprint server for biology · 2026Article
- Calcium signalling and organelle crosstalk in cardiovascular disease: an interplay of cardiac cell death pathways.Molecular biology reports · 2025Review
- CaBiomedicines · 2025Review
- Store-Operated CaJournal of clinical medicine · 2023Review
- Lysosomal calcium loading promotes spontaneous calcium release by potentiating ryanodine receptors.Biophysical journal · 2023Article
- Timing mechanisms to control heart rhythm and initiate arrhythmias: roles for intracellular organelles, signalling pathways and subsarcolemmal CaPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Function and Role of Histamine HPharmaceuticals (Basel, Switzerland) · 2023Review
- Effects of Apocynin, a NADPH Oxidase Inhibitor, in the Protection of the Heart from Ischemia/Reperfusion Injury.Pharmaceuticals (Basel, Switzerland) · 2023Article
- NAADP-Mediated CaHandbook of experimental pharmacology · 2023Article
- Neuromasts and Olfactory Organs of Zebrafish Larvae Represent Possible Sites of SARS-CoV-2 Pseudovirus Host Cell Entry.Journal of virology · 2022Article
- Two-pore channels: going with the flows.Biochemical Society transactions · 2022Article
- Review
- Targeting calcium-mediated inter-organellar crosstalk in cardiac diseases.Expert opinion on therapeutic targets · 2022Article
- Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular CaFrontiers in cell and developmental biology · 2022Article
- Oxidation of Protein Kinase A Regulatory Subunit PKARIα Protects Against Myocardial Ischemia-Reperfusion Injury by Inhibiting Lysosomal-Triggered Calcium Release.Circulation · 2021Article
- Targeting Endolysosomal Two-Pore Channels to Treat Cardiovascular Disorders in the Novel COronaVIrus Disease 2019.Frontiers in physiology · 2021Article
- Targeting Two-Pore Channels: Current Progress and Future Challenges.Trends in pharmacological sciences · 2020Review
Corrections and comments
- Commented on by
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
aimsIn the heart, a period of ischaemia followed by reperfusion evokes powerful cytosolic Ca(2+) oscillations that can cause lethal cell injury. These signals represent attractive cardioprotective targets, but the underlying mechanisms of genesis are ill-defined. Here, we investigated the role of the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP), which is known in several cell types to induce Ca(2+) oscillations that initiate from acidic stores such as lysosomes, likely via two-pore channels (TPCs, TPC1 and 2). METHODS AND
resultsAn NAADP antagonist called Ned-K was developed by rational design based on a previously existing scaffold. Ned-K suppressed Ca(2+) oscillations and dramatically protected cardiomyocytes from cell death in vitro after ischaemia and reoxygenation, preventing opening of the mitochondrial permeability transition pore. Ned-K profoundly decreased infarct size in mice in vivo. Transgenic mice lacking the endo-lysosomal TPC1 were also protected from injury.
conclusionNAADP signalling plays a major role in reperfusion-induced cell death and represents a potent pathway for protection against reperfusion injury.
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.