Abstract
GYY4137 is a hydrogen sulfide (H2S) donor that has been shown to act in an anti-inflammatory manner in vitro and in vivo. Microglial cells are among the major players in immunoinflammatory, degenerative, and neoplastic disorders of the central nervous system, including multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and glioblastoma multiforme. So far, the effects of GYY4137 on microglial cells have not been thoroughly investigated. In this study, BV2 microglial cells were stimulated with interferon-gamma and lipopolysaccharide and treated with GYY4137. The agent did not influence the viability of BV2 cells in concentrations up to 200 μM. It inhibited tumor necrosis factor but not interleukin-6 production. Expression of CD40 and CD86 were reduced under the influence of the donor. The phagocytic ability of BV2 cells and nitric oxide production were also affected by the agent. Surprisingly, GYY4137 upregulated generation of reactive oxygen species (ROS) by BV2 cells. The effect was mimicked by another H2S donor, Na2S, and it was not reproduced in macrophages. Our results demonstrate that GYY4137 downregulates inflammatory properties of BV2 cells but increases their ability to generate ROS. Further investigation of this unexpected phenomenon is warranted.
Highlights
Hydrogen sulfide (H2 S) is a gaseous signaling molecule that has anti-inflammatory and cytoprotective properties [1]
BV2 cells were stimulated with interferon-γ (IFN-γ) and lipopolysaccharide (LPS) and exposed to various concentrations of GYY4137
There was no effect on BV2 cell viability after 24 h of cultivation even with the highest concentration applied (200 μM), as deduced by crystal violet (CV)
Summary
Hydrogen sulfide (H2 S) is a gaseous signaling molecule that has anti-inflammatory and cytoprotective properties [1]. A role for H2 S has been hypothesized in glioblastoma multiforme (GBM) and neuroblastoma in light of the finding that the expression and activity of CBS, gamma-cystathionase (CTH, EC 4.4.1.1), and 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2) were found in the Molecules 2018, 23, 2966; doi:10.3390/molecules23112966 www.mdpi.com/journal/molecules. Molecules 2018, 23, 2966 human glioblastoma-astrocytoma (U-87 MG) and neuroblastoma (SHSY5Y) cell lines [6]. In both cell lines, the expression and activity of MPST was the highest among the investigated enzymes, suggesting its possible role in the generation of H2 S. The higher expression and activity of CBS, CTH, and MPST in the neuroblastoma cells were associated with more intensive generation of H2 S in the presence of 2 mM of cysteine. A threefold higher level of sulfane sulfur, a potential source of H2 S, was detected in the astrocytoma cells in comparison to the neuroblastoma cells [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
