ArticleCNS neuroscience & therapeutics2013
Zinc promotes the death of hypoxic astrocytes by upregulating hypoxia-induced hypoxia-inducible factor-1alpha expression via poly(ADP-ribose) polymerase-1.
Article in CNS neuroscience & therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Zinc Signaling in Acute Kidney Injury.Cells · 2026Review
- Kapβ2 Reverses Sevoflurane-Induced Hydrogel Phase Transition of hnRNPA2/B1-SG in Hypoxic Primary Rat Hippocampal Neurons.CNS neuroscience & therapeutics · 2025Article
- Research progress of hypoxia-inducible factor-1α and zinc in the mechanism of diabetic kidney disease.Frontiers in pharmacology · 2025Review
- Zinc enhances the cell adhesion, migration, and self-renewal potential of human umbilical cord derived mesenchymal stem cells.World journal of stem cells · 2023Article
- Characterisation of Primary Human Hippocampal Astrocyte Cell Culture Following Exposure to Hypoxia.The Malaysian journal of medical sciences : MJMS · 2023Article
- Zinc improves neurological recovery by promoting angiogenesis via the astrocyte-mediated HIF-1α/VEGF signaling pathway in experimental stroke.CNS neuroscience & therapeutics · 2022Article
- Zinc Accumulation Aggravates Cerebral Ischemia/Reperfusion Injury Through Inducing Endoplasmic Reticulum Stress.Neurochemical research · 2022Article
- MicroRNA-30a regulates acute cerebral ischemia-induced blood-brain barrier damage through ZnT4/zinc pathway.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Zinc cytotoxicity induces mitochondrial morphology changes in hela cell line.International journal of physiology, pathophysiology and pharmacology · 2021Article
- ROS-responsive capsules engineered from EGCG-Zinc networks improve therapeutic angiogenesis in mouse limb ischemia.Bioactive materials · 2021Article
- Excitotoxicity: Still Hammering the Ischemic Brain in 2020.Frontiers in neuroscience · 2020Review
- Acute Methylmercury Exposure and the Hypoxia-InducibleEnvironmental health perspectives · 2019Article
- Anti-ZnCellular and molecular neurobiology · 2018Article
- Targeting Sentinel Proteins and Extrasynaptic Glutamate Receptors: a Therapeutic Strategy for Preventing the Effects Elicited by Perinatal Asphyxia?Neurotoxicity research · 2018Review
- Gastrodin exerts robust neuroprotection in the postischemic brain via its protective effect against ZnAnimal cells and systems · 2018Article
- Time-Dependent Changes in Apoptosis Upon Autophagy Inhibition in Astrocytes Exposed to Oxygen and Glucose Deprivation.Cellular and molecular neurobiology · 2017Article
- Pathophysiological role of zinc in ischemic brain injury.Oncotarget · 2017Article
- Regeneration in the nervous system with erythropoietin.Frontiers in bioscience (Landmark edition) · 2016Review
- Reduction of zinc accumulation in mitochondria contributes to decreased cerebral ischemic injury by normobaric hyperoxia treatment in an experimental stroke model.Experimental neurology · 2015Article
- Autophagy Mediates Astrocyte Death During Zinc-Potentiated Ischemia--Reperfusion Injury.Biological trace element research · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
aimPathological release of excess zinc ions has been implicated in ischemic brain cell death. However, the underlying mechanisms remain to be elucidated. In stroke, ischemia-induced zinc release and hypoxia-inducible factor-1 (HIF-1) accumulation concurrently occur in the ischemic tissue. The present study tests the hypothesis that the presence of high intracellular zinc concentration is a major cause of modifications to PARP-1 and HIF-1α during hypoxia, which significantly contributes to cell death during ischemia.
methodsPrimary cortical astrocytes and C8-D1A cells were exposed to different concentrations of zinc chloride. Cell death rate and protein expression of HIF-1 and Poly(ADP-ribose) polymerase (PARP)-1 were examined after 3-h hypoxic treatment.
resultsAlthough 3-h hypoxia or 100 μM of zinc alone did not induce noticeable cytotoxicity, their combination led to a dramatic increase in astrocytic cell death in a zinc-concentration-dependent manner. Exposure of astrocytes to hypoxia for 3 h remarkably increased the levels of intracellular zinc and HIF-1α protein, which was further augmented by added exogenous zinc. Notably, HIF-1α knockdown blocked zinc-induced astrocyte death. Moreover, knockdown of PARP-1, another important protein in the response of hypoxia, attenuated the overexpression of HIF-1α and reduced the cell death rate.
conclusionsOur studies show that zinc promotes hypoxic cell death through overexpression of the hypoxia response factor HIF-1α via the cell fate determine factor PARP-1 modification, which provides a novel mechanism for zinc-mediated ischemic brain injury.
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