SBi4211 alleviates gp120-induced central nervous system injury via inhibiting S100B/ RAGE

Abstract

To explore the protective effect of SBi4211 (heptamidine), an inhibitor of S100B, against central nervous system injury induced by HIV-1 envelope protein gp120. In an in vitro model, U251 glioma cells were co-cultured with SH-SY5Y cells to explore the protective effect of SBi4211 against gp120-induced central nervous system injury. In a gp120 transgenic (Tg) mouse model (8 months old) mimicking HIV-associated neurocognitive disorder (HAND), the effect of treatment with gp120 or both gp120 and SBi4211 on neuronal activity and apoptosis were assessed using Cell Counting kit-8 (CCK-8) and flow cytometry. ELISA, Western blotting and immunohistochemistry were used to determine the expression levels of S100B, RAGE, GFAP, NeuN, Syn, MAP-2 and the inflammatory factors IL-6 and TNF-α. In the cell co-culture system, SBi4211 treatment significantly inhibited gp120-induced expression of S100B, RAGE and GFAP in U251 cells (P < 0.001), reduced the levels of inflammatory factors iNOS, IL-6 and TNF-α (P < 0.001) and enhanced the expressions of neuron-related proteins NeuN, Syn and MAP-2 (P < 0.001). In the transgenic mouse model, SBi4211 treatment significantly reduced the expressions of S100B, RAGE and inflammation levels (P < 0.05), inhibited the activation of astrocytes in the brain, and maintained the integrity of the neurons (P < 0.05). SBi4211 can protect neurons from gp120-induced neurotoxicity possibly by inhibiting the S100B/ RAGE-mediated signaling pathway.