ArticleThe Journal of clinical investigation2009
Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 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
246 citing papers in PubMed, 419 citations in OpenAlex.
- Trial
- A human-derived Pseudorabies virus isolate induces Cav2.2-sensitive CaMicrobiology spectrum · 2026Article
- Anti-Inflammatory Effect of Palmatine Chloride on Lipopolysaccharide-Stimulated RAW 264.7 Mouse Macrophages via Calcium-CHOP Pathway.International journal of molecular sciences · 2026Article
- NSD2 inhibits the expression of PD-L1 via oxidative phosphorylation to control immune surveillance in hepatocellular carcinoma.Cell death & disease · 2026Article
- Comparative Phosphoproteomics of TwoJournal of fungi (Basel, Switzerland) · 2026Article
- Article
- Modulation of ion channels as emerging therapeutic targets in the treatment of diabetic neuropathy.EXCLI journal · 2026Review
- The E3 ubiquitin ligase FBXL18 stabilizes BST2 to promote inflammation in RABV-infected astrocytes.Nature communications · 2025Article
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- 12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII.Nature communications · 2025Article
- Silver Needle Thermal Therapy Improves Mitochondrial Injury in the Skeletal Muscle of MPS Rats by Inhibiting the TRPV1/CaMKII Pathway.Physiological research · 2025Article
- Endoplasmic reticulum stress pathways and cellular death mechanisms in patients with phenylketonuria.Molecular biology reports · 2025Article
- SERCA-mediated endoplasmic reticulum stress facilitates hematopoietic stem cell mobilization.Stem cell research & therapy · 2025Article
- Filtering cells with high mitochondrial content depletes viable metabolically altered malignant cell populations in cancer single-cell studies.Genome biology · 2025Article
- Combination drug therapy prevents CIAKI by suppressing ER stress-induced apoptosis.Scientific reports · 2024Article
- Thapsigargin and its prodrug derivatives: exploring novel approaches for targeted cancer therapy through calcium signaling disruption.Medical oncology (Northwood, London, England) · 2024Review
- Potential of natural drug modulation of endoplasmic reticulum stress in the treatment of myocardial injury.Journal of pharmaceutical analysis · 2024Review
- Endoplasmic reticulum stress in diseases.MedComm · 2024Review
- Endoplasmic reticulum stress signaling modulates ischemia/reperfusion injury in the aged heart by regulating mitochondrial maintenance.Molecular medicine (Cambridge, Mass.) · 2024Review
186 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
ER stress-induced apoptosis is implicated in various pathological conditions, but the mechanisms linking ER stress-mediated signaling to downstream apoptotic pathways remain unclear. Using human and mouse cell culture and in vivo mouse models of ER stress-induced apoptosis, we have shown that cytosolic calcium resulting from ER stress induces expression of the Fas death receptor through a pathway involving calcium/calmodulin-dependent protein kinase IIgamma (CaMKIIgamma) and JNK. Remarkably, CaMKIIgamma was also responsible for processes involved in mitochondrial-dependent apoptosis, including release of mitochondrial cytochrome c and loss of mitochondrial membrane potential. CaMKII-dependent apoptosis was also observed in a number of cultured human and mouse cells relevant to ER stress-induced pathology, including cultured macrophages, endothelial cells, and neuronal cells subjected to proapoptotic ER stress. Moreover, WT mice subjected to systemic ER stress showed evidence of macrophage mitochondrial dysfunction and apoptosis, renal epithelial cell apoptosis, and renal dysfunction, and these effects were markedly reduced in CaMKIIgamma-deficient mice. These data support an integrated model in which CaMKII serves as a unifying link between ER stress and the Fas and mitochondrial apoptotic pathways. Our study also revealed what we believe to be a novel proapoptotic function for CaMKII, namely, promotion of mitochondrial calcium uptake. These findings raise the possibility that CaMKII inhibitors could be useful in preventing apoptosis in pathological settings involving ER stress-induced apoptosis.
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.