Environmental health perspectives
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Environ. Health Perspect. · Dec 2019
Acute Methylmercury Exposure and the Hypoxia-Inducible Factor- 1 α Signaling Pathway under Normoxic Conditions in the Rat Brain and Astrocytes in Vitro.
As a ubiquitous environmental pollutant, methylmercury (MeHg) induces toxic effects in the nervous system, one of its main targets. However, the exact mechanisms of its neurotoxicity have not been fully elucidated. Hypoxia-inducible factor- 1 α ( HIF- 1 α ), a transcription factor, plays a crucial role in adaptive and cytoprotective responses in cells and is involved in cell survival, proliferation, apoptosis, inflammation, angiogenesis, glucose metabolism, erythropoiesis, and other physiological activities. ⋯ MeHg induced a significant reduction in HIF- 1 α protein by activating proline hydroxylase (PHD) and the ubiquitin proteasome system (UPS) in primary rat astrocytes. Additionally, ROS scavenging by antioxidants played a neuroprotective role via increasing HIF- 1 α expression in response to MeHg toxicity. Moreover, we established that up-regulation of HIF- 1 α might serve to mitigate the acute toxicity of MeHg in astrocytes, affording a novel therapeutic target for future exploration. https://doi.org/10.1289/EHP5139.