ArticleFrontiers in neuroscience2019
Melatonin Prevents Mice Cortical Astrocytes From Hemin-Induced Toxicity Through Activating PKCα/Nrf2/HO-1 Signaling
Article in Frontiers in neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- The biological clock in parkinson's disease: mechanisms and chronotherapy.NPJ Parkinson's disease · 2026Review
- Melatonin Modulates Astrocyte Inflammatory Response and Nrf2/SIRT1 Signaling Pathways in Adult Rat Cortical Cultures.Biomedicines · 2025Article
- Interactions Between Ferroptosis and Oxidative Stress in Ischemic Stroke.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- Melatonin attenuates high glucose‑induced endothelial cell pyroptosis by activating the Nrf2 pathway to inhibit NLRP3 inflammasome activation.Molecular medicine reports · 2023Article
- Lipoxin alleviates oxidative stress: a state-of-the-art review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- Human-rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic-ischemic pathway melatonin-sensitive.Journal of pineal research · 2022Article
- Review
- Exogenous Melatonin Activating Nuclear Factor E2-Related Factor 2 (Nrf2) Pathway via Melatonin Receptor to Reduce Oxidative Stress and Apoptosis in Antler Mesenchymal Stem Cells.Molecules (Basel, Switzerland) · 2022Article
- Regulation of nuclear factor erythroid-2-related factor 2 as a potential therapeutic target in intracerebral hemorrhage.Frontiers in molecular neuroscience · 2022Review
- Oxidative Stress Following Intracerebral Hemorrhage: From Molecular Mechanisms to Therapeutic Targets.Frontiers in immunology · 2022Review
- Anti-Inflammatory Activity of Melatonin: a Focus on the Role of NLRP3 Inflammasome.Inflammation · 2021Review
- Neurovascular Units and Neural-Glia Networks in Intracerebral Hemorrhage: from Mechanisms to Translation.Translational stroke research · 2021Review
- Article
- Article
- Melatonin Suppresses Ferroptosis Induced by High Glucose via Activation of the Nrf2/HO-1 Signaling Pathway in Type 2 Diabetic Osteoporosis.Oxidative medicine and cellular longevity · 2020Article
- Nrf2 and Ferroptosis: A New Research Direction for Neurodegenerative Diseases.Frontiers in neuroscience · 2020Review
- Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Secondary injuries mediated by oxidative stress lead to deterioration of neurological functions after intracerebral hemorrhage (ICH). Cortical astrocytes are among the most important cells in the central nervous system (CNS), and play key roles in maintaining redox homeostasis by providing oxidative stress defense. Hemin is a product of hemoglobin degradation, which has strong toxicity and can induce reactive oxygen species (ROS). Melatonin (Mel) and its metabolites are well tolerated without toxicity, prevent tissue damage as well as effectively assist in scavenging free radicals. We evaluated the hemin neurotoxicity to astrocytes and the resistance of Mel-treated astrocytes to hemin neurotoxicity. And we found Mel induced PKCα phosphorylation (p-PKC), nuclear translocation of Nrf2 in astrocytes, and upregulation of HO-1, which contributed to the reduction of ROS accumulation and cell apoptosis. Nrf2 and HO1 protein expression upregulated by Mel were decreased after administration of PKC inhibitor, Ro 31-8220 (Ro 31). Luzindole (Luz), a melatonin receptor inhibitor, suppressed p-PKCα, HO-1, and Nrf2 expression upregulated by Mel and increased cell apoptosis rate. The upregulation of HO-1 induced by Mel was depressed by knocking down Nrf2 expression by siRNA, which also decreased the resistance of astrocytes to toxicity of hemin. Mel activates astrocytes through PKCα/Nrf2/HO-1 signaling pathway to acquire resistance to toxicity of hemin and resist from oxidative stress and apoptosis. The positive effect of Mel on PKCα/Nrf2/HO-1 signaling pathway may become a new target for neuroprotection after intracerebral hemorrhage.
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