Journal
TOXICOLOGY
Volume 408, Issue -, Pages 62-69Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2018.07.001
Keywords
Mercuric chloride; Hg (II)-serum albumin adduct; N9 microglial cell; Hormesis; Hg2+-binding site; Coordination structure
Categories
Funding
- National Nature Science Foundation of China [81374063]
- Key Laboratory Special Development Program of Qinghai Province [2017-ZJ-Y08]
- International Partnership Program of Chinese Academy of Sciences [153631KYSB20160004]
Ask authors/readers for more resources
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 (ID-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-alpha and IL-1 beta and inhibited cell proliferation. At high dosage (15 mu g/mL) we observed decline in NO and intracellular Ca2+ levels, and increment in the release of TNF-alpha and IL-1 beta. 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-co-ordination structure in Asp249 site is more stable than four-coordination structure in Cys34 site but four-co-ordination structure is formed easily in-vivo in consideration of binding-site position in spatial structure of HSA.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available