Modulation of Astrocytic Glutamine Synthetase by Endocannabinoid 2-Arachidonoylglycerol in JNK-Independent Pathway.

The glutamine synthetase (GS), an astrocyte-specific enzyme, plays an important role in neuroprotection through the glutamate/glutamine shuttle and can be modulated by endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) through extracellular signal-regulated protein kinase ½ (ERK1/2) and p38 signaling pathways. However, the role of c-Jun N-terminal kinase (JNK) signaling pathway in the modulation of GS in astrocytes by 2-AG is not clear. The expression of GS and JNK in astrocytes following the exposure to lipopolysaccharide (LPS) was examined with Western blotting and immunochemistry. The results revealed that short-term exposure to LPS activated GS and increased phosphorylation of JNK in astrocytes in a time-dependent manner. Treatment with 2-AG reversed the changes in GS but had no effect on the activation of JNK. These findings suggest that the activation of JNK induced by LPS is not involved in the modulation of astrocytic GS by 2-AG.