Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 81008, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China.
Toxicology. 2018 Sep 1;408:62-69. doi: 10.1016/j.tox.2018.07.001. Epub 2018 Jul 5.
Mercury chloride (HgCl), a neurotoxicant that cannot penetrate the blood-brain barrier (BBB). Although when the BBB are got damaged by neurodegenerative disorders, the absorbed HgCl, 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 Ca 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 Ca 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 Hg 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.
氯化汞（HgCl）是一种神经毒素，不能穿透血脑屏障（BBB）。尽管当 BBB 被神经退行性疾病破坏时，吸收的 HgCl 主要以人血浆中 Hg（II）-血清白蛋白加合物（Hg-HSA）的形式穿透 BBB 并影响中枢神经系统（CNS）细胞。目前的研究计划评估 Hg-HSA 对 N9 小胶质细胞生理功能的影响。在低剂量（15ng/mL）的 Hg-HAS 作用下，观察到的结果是：促进细胞增殖、一氧化氮（NO）和细胞内 Ca 水平增强，抑制 TNF-α和 IL-1β的释放并抑制细胞增殖。在高剂量（15μg/mL）下，我们观察到 NO 和细胞内 Ca 水平下降，以及 TNF-α和 IL-1β的释放增加。这些两相作用类似于适应现象，在这种情况下，适应现象是通过 ERK/MAPKs 和 JAK/STAT3 信号通路执行的。量子化学研究表明，Hg 可以在 HSA 的 Asp249 和 Cys34 位点形成稳定的配位结构。尽管 Asp249 位点的五配位结构比 Cys34 位点的四配位结构更稳定，但考虑到 HSA 空间结构中结合位点的位置，四配位结构在体内更容易形成。
