γ-Glutamylcysteine Ameliorates LPS-Induced Inflammatory Responses in BV2 Cells via Activating Autophagy

Abstract

In neurodegenerative diseases, the activation of microglia and the ensuing neuroinflammation are pivotal in regulating disease progression. Attenuating inflammation induced by microglial cells is considered a key strategy for slowing the progression of neurodegenerative diseases. γ-glutamylcysteine (γ-GC) has exhibited significant antioxidative and anti-inflammatory effects; nevertheless, its potential role in modulating neuroinflammatory responses remains incompletely explored. The current investigation aimed to establish a neuroinflammation model by stimulating BV2 microglia cells with lipopolysaccharide (LPS) and to explore the protective effect of γ-GC on neuroinflammation in BV2 microglia cells. The results demonstrated that γ-GC significantly attenuated LPS-induced oxidative damage in BV2 cells, reduced the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), inhibited the cytoplasmic translocation of high-mobility group box 1 protein (HMGB1), and effectively mitigated the LPS-induced inflammatory response in BV2 cells. We further investigated the regulatory mechanism of γ-GC on LPS-induced BV2 neuroinflammation and found that γ-GC significantly enhances autophagy in BV2 cells, resulting in a marked reduction in mammalian target of rapamycin (mTOR) phosphorylation levels and an increase in AMP-activated protein kinase (AMPK) phosphorylation levels. The use of autophagy inhibitors 3-methyladenine (3-MA) and AMPK inhibitors further corroborates the proposition that γ-GC promotes autophagy in BV2 cells while suppressing the LPS-induced inflammatory response of BV2 microglia through the activation of the AMPK-mTOR pathway. The findings indicate that γ-GC exerts a substantial inhibitory impact on neuroinflammation, making it a promising candidate for the development of therapeutic strategies against neuroinflammatory disorders and related conditions.