Hydrogen sulphide ameliorates dopamine-induced astrocytic inflammation and neurodegeneration in minimal hepatic encephalopathy.

Abstract

It has been demonstrated that the action of dopamine (DA) could enhance the production of tumour necrosis factor-α (TNF-α) by astrocytes and potentiate neuronal apoptosis in minimal hepatic encephalopathy (MHE). Recently, sodium hydrosulfide (NaHS) has been found to have neuroprotective properties. Our study addressed whether NaHS could rescue DA-challenged inflammation and apoptosis in neurons to ameliorate memory impairment in MHE rats and in the neuron and astrocyte coculture system. We found that NaHS suppressed DA-induced p65 acetylation, resulting in reduced TNF-α production in astrocytes both in vitro and in vivo. Furthermore, decreased apoptosis was observed in neurons exposed to conditioned medium from DA + NaHS-challenged astrocytes, which was similar to the results obtained in the neurons exposed to TNF-α + NaHS, suggesting a therapeutic effect of NaHS on the suppression of neuronal apoptosis via the reduction of TNF-α level. DA triggered the inactivation of p70 S6 ribosomal kinase (S6K1) and dephosphorylation of Bad, resulting in the disaggregation of Bclxl and Bak and the release of cytochrome c (Cyt. c), and this process could be reversed by NaHS administration. Our work demonstrated that NaHS attenuated DA-induced astrocytic TNF-α release and ameliorated inflammation-induced neuronal apoptosis in MHE. Further research into this approach may uncover future potential therapeutic strategies for MHE.

• Authors: Weishan Zhuge, Qichuan Zhuge, Weikan Wang, Xiaoai Lu, Ruimin You, Leping Liu, He Yu, Jian Wang, Xuebao Wang, Yiru Ye, Saidan Ding
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 23 Pg. 13634-13647 (12 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 33118312 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Bad protein, rat
• Bcl2l1 protein, rat
• Biomarkers
• Tumor Necrosis Factor-alpha
• bcl-Associated Death Protein
• bcl-X Protein
• Dopamine
• Hydrogen Sulfide

Topics

• Animals
• Apoptosis (drug effects)
• Astrocytes (drug effects, metabolism)
• Behavior, Animal (drug effects)
• Biomarkers
• Brain (drug effects, metabolism, pathology)
• Cognition (drug effects)
• Cognitive Dysfunction (drug therapy, etiology, metabolism)
• Disease Susceptibility
• Dopamine (adverse effects, metabolism)
• Hepatic Encephalopathy (complications, metabolism, pathology)
• Hydrogen Sulfide (pharmacology)
• Neurodegenerative Diseases (drug therapy, etiology, metabolism, pathology)
• Neurons (drug effects, metabolism)
• Phosphorylation (drug effects)
• Protein Binding
• Rats
• Tumor Necrosis Factor-alpha (metabolism)
• bcl-Associated Death Protein (metabolism)
• bcl-X Protein (metabolism)