ArticleNeuropharmacology2009
Heme oxygenase activity and hemoglobin neurotoxicity are attenuated by inhibitors of the MEK/ERK pathway.
Article in Neuropharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 22 citations in OpenAlex.
- Renin-angiotensin system blockade attenuates brain mitochondrial dysfunction, oxidative stress, and neuroinflammation associated with hypertension, metabolic disorders, and aging.World journal of experimental medicine · 2026Review
- Neuroprotection after Hemorrhagic Stroke Depends on Cerebral Heme Oxygenase-1.Antioxidants (Basel, Switzerland) · 2019Article
- Mitigating effect of biotin against irradiation-induced cerebral cortical and hippocampal damage in the rat brain tissue.Environmental science and pollution research international · 2019Article
- Intracellular FeScientific reports · 2019Article
- Haptoglobin increases the vulnerability of CD163-expressing neurons to hemoglobin.Journal of neurochemistry · 2016Article
- Oxidative Stress in Intracerebral Hemorrhage: Sources, Mechanisms, and Therapeutic Targets.Oxidative medicine and cellular longevity · 2016Review
- New insights into intracellular locations and functions of heme oxygenase-1.Antioxidants & redox signaling · 2014Review
- Progress in translational research on intracerebral hemorrhage: is there an end in sight?Progress in neurobiology · 2014Review
- Transplantation of neural stem cells that overexpress SOD1 enhances amelioration of intracerebral hemorrhage in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2014Article
- Methemoglobin-induced signaling and chemokine responses in human alveolar epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- Hydrogen peroxide and extracellular signal-related kinase 1/2 pathway regulate ferritin levels in retinal pigmented and lens epithelial cells.Molecular vision · 2013Article
- Effect of iron chelators on methemoglobin and thrombin preconditioning.Translational stroke research · 2012Article
- Hemopexin decreases hemin accumulation and catabolism by neural cells.Neurochemistry international · 2012Article
- Enhanced striatal cholinergic neuronal activity mediates L-DOPA-induced dyskinesia in parkinsonian mice.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Multi-gram scale synthesis of FR180204.The Journal of organic chemistry · 2009Article
- Apotransferrin protects cortical neurons from hemoglobin toxicity.NeuropharmacologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Hemoglobin breakdown produces an iron-dependent neuronal injury after experimental CNS hemorrhage that may be attenuated by heme oxygenase (HO) inhibitors. The HO enzymes are phosphoproteins that are activated by phosphorylation in vitro. While testing the effect of kinase inhibitors in cortical cell cultures, we observed that HO activity was consistently decreased by the MEK inhibitor U0126. The present study tested the hypothesis that MEK/ERK pathway inhibitors reduce HO activity and neuronal vulnerability to hemoglobin. The MEK inhibitors U0126 and SL327 and the ERK inhibitor FR180204 reduced baseline culture HO activity by 35-50%, without altering the activity of recombinant HO-1 or HO-2; negative control compounds U0124 and FR180289 had no effect. Hemoglobin exposure for 16h produced widespread neuronal injury, manifested by release of 59.2+/-7.8% of neuronal lactate dehydrogenase and a twelve-fold increase in malondialdehyde; kinase inhibitors were highly protective. HO-1 induction after hemoglobin treatment was also decreased by U0126, SL327, and FR180204. These results suggest that reduction in HO activity may contribute to the protective effect of MEK and ERK inhibitors against heme-mediated neuronal 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.