ArticleJournal of cellular physiology2009
Activation of GABA-A receptor ameliorates homocysteine-induced MMP-9 activation by ERK pathway.
Article in Journal of cellular physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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.
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Who cites it
38 citing papers in PubMed, 71 citations in OpenAlex.
- Hyperhomocysteinemia-Driven Ischemic Stroke: Unraveling Molecular Mechanisms and Therapeutic Horizons.Food science & nutrition · 2025Review
- Epigenetics of Homocystinuria, Hydrogen Sulfide, and Circadian Clock Ablation in Cardiovascular-Renal Disease.Current issues in molecular biology · 2024Review
- Increases in 4-Acetaminobutyric Acid Generated by Phosphomevalonate Kinase Suppress CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Homocysteine Promotes Intestinal Inflammation in Colitis Mice Through the PGE2/STAT3 Signaling Pathway.Digestive diseases and sciences · 2024Article
- Genome-wide interaction analysis of folate for colorectal cancer risk.The American journal of clinical nutrition · 2023Article
- Homocysteine-Potential Novel Diagnostic Indicator of Health and Disease in Horses.Animals : an open access journal from MDPI · 2023Review
- Higher serum homocysteine levels are associated with an increased risk of hemorrhagic transformation in patients with acute ischemic stroke.BMC neurology · 2023Article
- Novel mechanism of the COVID-19 associated coagulopathy (CAC) and vascular thromboembolism.Npj viruses · 2023Article
- Pleiotropic endophenotypic and phenotype effects of GABAergic neurosteroid synthesis deficiency in posttraumatic stress disorder.Current opinion in endocrine and metabolic research · 2022Article
- A role for deficits in GABAergic neurosteroids and their metabolites with NMDA receptor antagonist activity in the pathophysiology of posttraumatic stress disorder.Journal of neuroendocrinology · 2022Review
- Involvements of Hyperhomocysteinemia in Neurological Disorders.Metabolites · 2021Review
- The association between retinal vessel abnormalities and H-type hypertension.BMC neurology · 2021Article
- Homocysteine Level and Risk of Hemorrhage in Brain Arteriovenous Malformations.Disease markers · 2021Article
- Low Serum Uric Acid Levels Promote Hypertensive Intracerebral Hemorrhage by Disrupting the Smooth Muscle Cell-Elastin Contractile Unit and Upregulating the Erk1/2-MMP Axis.Translational stroke research · 2020Article
- Prognostic Significance of Homocysteine Level on Neurological Outcome in Brain Arteriovenous Malformations.Disease markers · 2020Article
- Exercise mitigates the effects of hyperhomocysteinemia on adverse muscle remodeling.Physiological reports · 2018Article
- Hypermethylation: Causes and Consequences in Skeletal Muscle Myopathy.Journal of cellular biochemistry · 2017Review
- Rhein and rhubarb similarly protect the blood-brain barrier after experimental traumatic brain injury via gp91Scientific reports · 2016Article
- The Molecular and Cellular Effect of Homocysteine Metabolism Imbalance on Human Health.International journal of molecular sciences · 2016Review
- Hyperhomocysteinemia, MMPs and Cochlear Function: A Short Review.Indian journal of clinical biochemistry : IJCB · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hyperhomocysteinemia (HHcy) is a risk factor for neuroinflammatory and neurodegenerative diseases. Homocysteine (Hcy) induces redox stress, in part, by activating matrix metalloproteinase-9 (MMP-9), which degrades the matrix and leads to blood-brain barrier dysfunction. Hcy competitively binds to gamma-aminbutyric acid (GABA) receptors, which are excitatory neurotransmitter receptors. However, the role of GABA-A receptor in Hcy-induced cerebrovascular remodeling is not clear. We hypothesized that Hcy causes cerebrovascular remodeling by increasing redox stress and MMP-9 activity via the extracellular signal-regulated kinase (ERK) signaling pathway and by inhibition of GABA-A receptors, thus behaving as an inhibitory neurotransmitter. Hcy-induced reactive oxygen species production was detected using the fluorescent probe, 2'-7'-dichlorodihydrofluorescein diacetate. Hcy increased nicotinamide adenine dinucleotide phosphate-oxidase-4 concomitantly suppressing thioredoxin. Hcy caused activation of MMP-9, measured by gelatin zymography. The GABA-A receptor agonist, muscimol ameliorated the Hcy-mediated MMP-9 activation. In parallel, Hcy caused phosphorylation of ERK and selectively decreased levels of tissue inhibitors of metalloproteinase-4 (TIMP-4). Treatment of the endothelial cell with muscimol restored the levels of TIMP-4 to the levels in control group. Hcy induced expression of iNOS and decreased eNOS expression, which lead to a decreased NO bioavailability. Furthermore muscimol attenuated Hcy-induced MMP-9 via ERK signaling pathway. These results suggest that Hcy competes with GABA-A receptors, inducing the oxidative stress transduction pathway and leading to ERK activation.
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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.