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Hormesis of mercuric chloride-human serum albumin adduct on N9 microglial cells via the ERK/MAPKs and JAK/STAT3 signaling pathways
TOX Toxicology
Format: Journal Article
Publication Year: 2018
Pages: 62 - 69
Source ID: shanti-sources-104346
Abstract:
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• Mercuric chloride-human serum albumin adduct causes hormesis in N9 microglia cells. • Hormesis was implemented through ERK/MAPKs and JAK/STAT3 signaling pathways. • 15 ng/mL of Hg-HSA was close to a NOAEL for N9 cells and this dose may be beneficial. • Hg2+ could form stable coordination structures in both Asp249 site and Cys34 site of HSA.
Mercury chloride (HgCl2), a neurotoxicant that cannot penetrate the blood-brain barrier (BBB). Although when the BBB are got damaged by neurodegenerative disorders, the absorbed HgCl2, mainly in form of Hg (II)-serum albumin adduct (Hg-HSA) in human plasma, can penetrate BBB and affect central nervous system (CNS) cells. Current study planned to evaluate the effect of Hg-HSA on the physiological function of N9 microglial cells. At low dosage (15 ng/mL) of Hg-HAS, the observed outcomes was: promoted cell propagation, Nitric Oxide (NO) and intracellular Ca2+ levels enhancement, suppressed the release of TNF-α and IL-1β and inhibited cell proliferation. At high dosage (15 μg/mL) we observed decline in NO and intracellular Ca2+ levels, and increment in the release of TNF-α and IL-1β. These biphasic effects are similar to hormesis, and the hormesis, in this case, was executed through ERK/MAPKs and JAK/STAT3 signaling pathways. Study of quantum chemistry revealed that Hg2+ could form stable coordination structures in both Asp249 and Cys34 sites of HSA. Although five-coordination structure in Asp249 site is more stable than four-coordination structure in Cys34 site but four-coordination structure is formed easily in-vivo in consideration of binding-site position in spatial structure of HSA.