Abstract
BackgroundThe glutamine synthetase (GS), an astrocyte-specific enzyme, is involved in lipopolysaccharide (LPS)-induced inflammation which activates the mitogen-activated protein kinase (MAPK) signaling. Endocannabinoid 2-arachidonyl glycerol (2-AG) has been described to serve as an endogenous mediator of analgesia and neuroprotection. However, whether 2-AG can directly influence astrocytic GS and MAPK expressions remains unknown.MethodsIn the present study, the effects of 2-AG on astrocytic GS expression, p38 and ERK1/2 expression, cell viability, and apoptosis following LPS exposure were investigated.ResultsThe results revealed that LPS exposure increased GS expression with p38 activation in the early phase and decreased GS expression with activation of ERK1/2, decrease of cell viability, and increase of apoptosis in the late phase. Inhibition of p38 reversed GS increase in the early phase while inhibition of ERK1/2 reversed GS decrease in the late phase induced by LPS exposure. 2-AG protected astrocytes from increase of apoptosis and decrease of cell viability induced by the late phase of LPS exposure. In the early phase of LPS exposure, 2-AG could suppress the increase of GS expression and activation of p38 signaling. In the late phase of LPS exposure, 2-AG could reverse the decrease of GS expression and activation of ERK1/2 induced by LPS.ConclusionThese findings suggest that 2-AG could maintain the GS expression in astrocytes to a relatively stable level through modulating MAPK signaling and protect astrocytes from LPS exposure.
Highlights
The glutamine synthetase (GS), an astrocyte-specific enzyme, is involved in lipopolysaccharide (LPS)induced inflammation which activates the mitogen-activated protein kinase (MAPK) signaling
The results indicated that LPS exposure induced time-dependent biphasic changes of GS expression in astrocytes; i.e., compared with control (1.00 ± 0.07 for 0 min), GS expression began to increase at 30 min (2.26 ± 0.06, p < 0.001), peaked at 1 h (3.15 ± 0.10, p < 0.001), declined to control level at 3 h (1.12 ± 0.10, p > 0.05), and decreased at 6 h (0.32 ± 0.05, p < 0.01), 12 h (0.18 ± 0.02, p < 0.001), and 24 h (0.06 ± 0.03, p < 0.001)
The present study indicated that p38 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were activated and translocated into nucleus in astrocytes by LPS exposure with different patterns, i.e., p38 was firstly activated at 30 min and reached peak at 2 h while ERK1/2 activated at 1 h and reached peak at 3 h, while inhibition of p38 and ERK1/2 attenuated the changes of GS expression induced by LPS
Summary
The glutamine synthetase (GS), an astrocyte-specific enzyme, is involved in lipopolysaccharide (LPS)induced inflammation which activates the mitogen-activated protein kinase (MAPK) signaling. Whether 2-AG can directly influence astrocytic GS and MAPK expressions remains unknown. Wang et al Journal of Neuroinflammation (2018) 15:220 whether 2-AG could directly modulate the GS expression in astrocytes, and the exact molecular mechanism remains unknown. The mitogen-activated protein kinase (MAPK) cascades are a family of serine/threonine kinases that can mediate a wide variety of extracellular stimuli into the cytoplasm and nuclei and regulate cellular gene expression and protein synthesis [17]. Previous studies have indicated that MAPK members, extracellular signal-regulated protein kinase 1/2 (ERK1/2) and p38 pathways, in astrocytes may be involved in the process of various neurological disorders [18]. Activation of ERK1/2 and p38 in cortical astrocytes has been identified in several neurodegenerative diseases, while blockade of ERK1/2 and p38 pathways has been shown to alleviate inflammation and clinical features in different animal models [20,21,22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
