ArticleBrain research2009
Estrogen attenuates glutamate-induced cell death by inhibiting Ca2+ influx through L-type voltage-gated Ca2+ channels.
Article in Brain research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Hirsutine, an Emerging Natural Product with Promising Therapeutic Benefits: A Systematic Review.Molecules (Basel, Switzerland) · 2023Pooled it
- Effects of tocolysis with nifedipine or atosiban on child outcome: follow-up of the APOSTEL III trial.BJOG : an international journal of obstetrics and gynaecology · 2020Trial
- Beyond Estrogen: Unraveling the Complexities of Hormonal Signaling Pathways in Alzheimer's Disease and Their Implications for Precision Therapy.Molecular neurobiology · 2025Review
- The Role of Estrogen in Brain MicroRNAs Regulation.Advanced pharmaceutical bulletin · 2024Review
- The Limited Effects of Estradiol Administration Immediately after Spinal Cord Injury.Puerto Rico health sciences journal · 2023Article
- Estrogen antagonizes ASIC1a-induced chondrocyte mitochondrial stress in rheumatoid arthritis.Journal of translational medicine · 2022Article
- Review
- Premarin Reduces Neurodegeneration and Promotes Improvement of Function in an Animal Model of Spinal Cord Injury.International journal of molecular sciences · 2022Article
- Steroid Sulfation in Neurodegenerative Diseases.Frontiers in molecular biosciences · 2022Review
- Regional Diversities in Fibrogenesis Weighed as a Key Determinant for Atrial Arrhythmogenesis.Biomedicines · 2021Review
- Nanoparticle-Based Estrogen Delivery to Spinal Cord Injury Site Reduces Local Parenchymal Destruction and Improves Functional Recovery.Journal of neurotrauma · 2021Article
- The Aging GABAergic System and Its Nutritional Support.Journal of nutrition and metabolism · 2021Review
- Predominance of Heart Failure With Preserved Ejection Fraction in Postmenopausal Women: Intra- and Extra-Cardiomyocyte Maladaptive Alterations Scaffolded by Estrogen Deficiency.Frontiers in cell and developmental biology · 2021Review
- Estrogen Protects Articular Cartilage by Downregulating ASIC1a in Rheumatoid Arthritis.Journal of inflammation research · 2021Article
- The Role of Estradiol in Traumatic Brain Injury: Mechanism and Treatment Potential.International journal of molecular sciences · 2020Review
- Response to pregabalin and progesterone differs in male and female rat models of neuropathic and cancer pain.Canadian journal of pain = Revue canadienne de la douleur · 2020Article
- Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy.Frontiers in pharmacology · 2020Review
- Article
- Estrogen receptor α promotes Cav1.2 ubiquitination and degradation in neuronal cells and in APP/PS1 mice.Aging cell · 2019Article
- Effects of Female Sex Steroids Administration on Pathophysiologic Mechanisms in Traumatic Brain Injury.Translational stroke research · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Estrogen-mediated neuroprotection is observed in neurodegenerative disease and neurotrauma models; however, determining a mechanism for these effects has been difficult. We propose that estrogen may limit cell death in the nervous system tissue by inhibiting increases in intracellular free Ca(2+). Here, we present data using VSC 4.1 cell line, a ventral spinal motoneuron and neuroblastoma hybrid cell line. Treatment with 1 mM glutamate for 24 h induced apoptosis. When cells were pre-treated with 100 nM 17beta-estradiol (estrogen) for 1 h and then co-treated with glutamate, apoptotic death was significantly attenuated. Estrogen also prevented glutamate-mediated changes in resting membrane potential and membrane capacitance. Treatment with either 17 alpha-estradiol or cell impermeable estrogen did not mimic the findings seen with estrogen. Glutamate treatment significantly increased both intracellular free Ca(2+) and the activities of downstream proteases such as calpain and caspase-3. Estrogen attenuated both the increases in intracellular free Ca(2+) and protease activities. In order to determine the pathway responsible for estrogen-mediated inhibition of these increases in intracellular free Ca(2+), cells were treated with several Ca(2+) entry inhibitors, but only the L-type Ca(2+) channel blocker nifedipine demonstrated cytoprotective effects comparable to estrogen. To expand these findings, cells were treated with the L-type Ca(2+) channel agonist FPL 64176, which increased both cell death and intracellular free Ca(2+), and estrogen inhibited both effects. From these observations, we conclude that estrogen limits glutamate-induced cell death in VSC 4.1 cells through effects on L-type Ca(2+) channels, inhibiting Ca(2+) influx as well as activation of the pro-apoptotic proteases calpain and caspase-3.
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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.