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Publication Detail

Title: Curcumin protects against methylmercury-induced cytotoxicity in primary rat astrocytes by activating the Nrf2/ARE pathway independently of PKCδ.

Authors: Yang, Bobo; Yin, Changsheng; Zhou, Yun; Wang, Qiang; Jiang, Yuanyue; Bai, Yu; Qian, Hai; Xing, Guangwei; Wang, Suhua; Li, Fang; Feng, Yun; Zhang, Yubin; Cai, Jiyang; Aschner, Michael; Lu, Rongzhu

Published In Toxicology, (2019 09 01)

Abstract: Methylmercury (MeHg) is a ubiquitous environmental toxicant that leads to long-lasting neurological deficits in animals and humans. Curcumin, a polyphenol obtained from the rhizome of turmeric, has well-known antioxidant functions. Here, we evaluated curcumin's efficacy in mitigating MeHg-induced cytotoxicity and further investigated the underlying mechanism of this neuroprotection in primary rat astrocytes. Pretreatment with curcumin (2, 5, 10 and 20 μM for 3, 6, 12 or 24 h) protected against MeHg-induced (5 μM for 6 h) cell death in a time and dose-dependent manner. Curcumin (2, 5, 10 or 20 μM) pretreatment for 12 h significantly ameliorated the MeHg-induced astrocyte injury and oxidative stress, as evidenced by morphological alterations, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, and glutathione (GSH) and catalase (CAT) levels. Moreover, curcumin pretreatment increased Nrf2 nuclear translocation and downstream enzyme expression, heme oxygenase-1 (HO-1) and NADPH quinone reductase-1 (NQO1). Knockdown of Nrf2 with siRNA attenuated the protective effect of curcumin against MeHg-induced cell death. However, both the pan-protein kinase C (PKC) inhibitor, Ro 31-8220, and the selective PKCδ inhibitor, rottlerin, failed to suppress the curcumin-activated Nrf2/Antioxidant Response Element(ARE) pathway and attenuate the protection exerted by curcumin. Taken together, these findings confirm that curcumin protects against MeHg-induced neurotoxicity by activating the Nrf2/ARE pathway and this protection is independent of PKCδ activation. More studies are needed to understand the mechanisms of curcumin cytoprotection.

PubMed ID: 31330227 Exiting the NIEHS site

MeSH Terms: Acetophenones/pharmacology; Animals; Antioxidant Response Elements/genetics*; Astrocytes/drug effects*; Benzopyrans/pharmacology; Curcumin/pharmacology*; Dose-Response Relationship, Drug; Fluorescent Antibody Technique; Glutathione/metabolism; Hylobatidae; Indoles/pharmacology; L-Lactate Dehydrogenase/metabolism; Methylmercury Compounds/antagonists & inhibitors; Methylmercury Compounds/toxicity*; NF-E2-Related Factor 2/metabolism*; Neuroprotective Agents/pharmacology*; Oxidative Stress/drug effects; Protein Kinase C-delta/metabolism; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species/metabolism; Signal Transduction/drug effects*

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