ArticleJournal of neurochemistry2008
Lysosomal release of cathepsins causes ischemic damage in the rat hippocampal slice and depends on NMDA-mediated calcium influx, arachidonic acid metabolism, and free radical production.
Article in Journal of neurochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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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.
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Who cites it
44 citing papers in PubMed, 88 citations in OpenAlex.
- SARS-CoV-2 Delta variant-specific ORF3a mutations destabilize lysosomal homeostasis to trigger lysosomal damage-mediated cell death.Communications biology · 2026Article
- The zinc-nitric oxide axis in acute brain injury: Convergent oxidative-nitrative stress, peroxynitrite signaling, and therapeutic targets.Redox biology · 2026Review
- AS1842856 Reduces β-Amyloid Burden via Inhibiting PLA2G4A-Mediated Lysosomal Dysfunction in APP/PS1 Mice.CNS neuroscience & therapeutics · 2026Article
- Underlying Mechanism of Lysosomal Membrane Permeabilization in CNS Injury: A Literature Review.Molecular neurobiology · 2025Review
- Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution.Cellular and molecular life sciences : CMLS · 2024Article
- Involvement of histone methylation in the regulation of neuronal death.Journal of physiology and biochemistry · 2023Review
- Distinct Cleavage Properties of Cathepsin B Compared to Cysteine Cathepsins Enable the Design and Validation of a Specific Substrate for Cathepsin B over a Broad pH Range.Biochemistry · 2023Article
- Quercetin's Effects on Glutamate Cytotoxicity.Molecules (Basel, Switzerland) · 2022Review
- The Complex Mechanisms by Which Neurons Die Following DNA Damage in Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- New multienzymatic complex formed between human cathepsin D and snake venom phospholipase AThe journal of venomous animals and toxins including tropical diseases · 2022Article
- How cytosolic compartments play safeguard functions against neuroinflammation and cell death in cerebral ischemia.Metabolic brain disease · 2021Review
- Selective Neutral pH Inhibitor of Cathepsin B Designed Based on Cleavage Preferences at Cytosolic and Lysosomal pH Conditions.ACS chemical biology · 2021Article
- Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy.Frontiers in molecular neuroscience · 2021Review
- Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics.International journal of nanomedicine · 2021Review
- N-Methyl-D-Aspartate Receptor Signaling-Protein Kinases Crosstalk in Cerebral Ischemia.Advances in experimental medicine and biology · 2021Article
- Cathepsin B in neurodegeneration of Alzheimer's disease, traumatic brain injury, and related brain disorders.Biochimica et biophysica acta. Proteins and proteomics · 2020Review
- The Lysosomal Membrane Protein Lamp2 Alleviates Lysosomal Cell Death by Promoting Autophagic Flux in Ischemic Cardiomyocytes.Frontiers in cell and developmental biology · 2020Article
- CaMKII/proteasome/cytosolic calcium/cathepsin B axis was present in tryspin activation induced by nicardipine.Bioscience reports · 2019Article
- cPLA2 activation contributes to lysosomal defects leading to impairment of autophagy after spinal cord injury.Cell death & disease · 2019Article
- Neuronal Cell Death.Physiological reviews · 2018Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
NMDA-mediated calcium entry and reactive oxygen species (ROS) production are well-recognized perpetrators of ischemic neuronal damage. The current studies show that these events lead to the release of the protein hydrolase, cathepsin B, from lysosomes 2 h following 5-min oxygen-glucose deprivation in the rat hippocampal slice. This release reflects a lysosomal membrane permeabilization (LMP) and was measured as the appearance of diffuse immunolabeled cathepsin B in the cytosol of CA1 pyramidal neurons. Necrotic neuronal damage begins after the release of cathepsins and is prevented by inhibitors of either cathepsin B or D indicating that the release of cathepsins is an important mediator of severe damage. There was an increase in superoxide levels, measured by dihydroethidium fluorescence, at the same time as LMP and reducing ROS levels with antioxidants, Trolox or N-tert-butyl-alpha-phenyl nitrone, blocked LMP. Both LMP and ROS production were blocked by an NMDA channel blocker (MK-801) and by inhibitors of mitogen-activated protein kinase kinase (U0126), calcium-dependent/independent phospholipases A2 (methyl arachidonyl fluorophosphonate) but not calcium-independent phospholipases A2 (bromoenol lactone) and cyclooxygenase-2 (NS398). A cell-permeant specific inhibitor of calpain (PD150606) prevented LMP, but not ROS production. It is concluded that LMP results in part from calcium-initiated and extracellular signal-regulated kinase-initiated arachidonic acid metabolism, which produces free radicals; it also requires the action of calpain.
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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.