Behavioral defects induced by chronic social defeat stress are protected by momordica charantia polysaccharides via attenuation of JNK3/PI3K/AKT neuroinflammatory pathway / 中国药理学与毒理学杂志

OBJECTIVE The aim of the present study was to evaluate the protective effects of momordica charantia polysaccharides(MCP)on depressive animal model induced by chronic social defeat stress(CSDS)and explore the underlying mechanisms.METHODS We established CSDS depressant mouse model and treated CSDS mice with MCP.Sucrose preference,forced swim test(FST)and social interaction test(SIT)were used to measure behaviors changes.We used ELISA,Q-PCR and western blot to test the levels of cytokines in the hippocampus. RESULTS The results showed that chronic administration of MCP(100,200 and 400 mg·kg-1)significantly prevented depressive-like behaviors in mice as assessed by social interaction (SIT), tail suspension (TST) and sucrose preference tests (SPT).It was showed that the elevation of proinflammatory cytokines(TNF-α,IL-6,and IL-β)concentra-tions,up-regulation of JNK3,c-Jun,and P-110β protein expressions in the hippocampus of CSDS model. Moreover,reduction activity of PI3K and phosphorylation level of protein kinase B(AKT)was also observed in the hippocampus of CSDS model.All above phenomenon were reversed after MCP intervened.Further-more,the protective effects of MCP on the CSDS mice were partly inhibited by the specific phosphati-dylinositol 3-kinase (PI3K)inhibitor, LY294002. CONCLUSION The protective effects of MCP against depressive-like effects in CSDS mice might reduce neuroinflammatory and involve in attenuation of JNK3/PI3K/AKT pathway in the hippocampus.

The Expression Changes of JNK3 and APP Protein in Apoptosis of Retinal Ganglion Cells after Optic Nerve Injury / 昆明医科大学学报

Objective To investigate the changes in the expression of JNK3 and APP protein in retinal ganglion cells (RGCs) after optic nerve injury and its effect on the survival of RGCs. Methods Optic nerve crush models were established using adult APP wild type mice. Immunohistochemistry and western blot for detecting the expression of JNK3 and APP protein in RGCs were used post-injury. The number of RGCs in APP KO mice group was counted to compare with APP WT mice group. Results After optic nerve injury, JNK3 expressed in cytoplasm of RGCs; p-JNK transformed from cytoplasm to nuclei of RGCs; APP expressed in cytomembrane; p-APP expressed in cytoplasm and axons of RGCs. Western blot results showed that the protein expressions of JNK3, p-JNK, APP and p-APP were increased in the injured group (P＜0.01) . The survival number of RGCs (147± 7.0) in APP KO mice group increased significantly than APP WT mice group (127.7 ±7.0) (P＜0.05) . Conclusion The upregulation of JNK3 and APP protein expression maybe play an important role in RGCs survival proceeds after optic nerve injury.

The Role of JNK kinase in apoptosis and its relationship with cancer / 中国药理学通报

JNK is a key protein in the third stages of MAPK pro-tein kinase activation cascade,and is located in the key node of multiple signal transduction network.It plays a pivotal role in the cell proliferation,differentiation,apoptosis and some other important cell biological processes.Therefore it acts as an im-portant factor in regulating the development of some major human diseases,such as cancer.But the functional diversity and com-plexity of three JNK isoforms in different cell types make it diffi- cult to develop anticancer drugs with JNK as a treatment target. In this review,we summarized the apoptotic signaling network of JNK and the regulation functions of JNK in cell apoptosis and proliferation.We also discuss the different functions of 3 JNK isoforms in human cancer.