c-Jun氨基末端激酶信号转导途径与胰岛β细胞凋亡

c-Jun N-terminal kinases (JNK) is one of the important members of mitogen activated protein kinase family. JNK pathway participates in the apoptosis of pancreatic beta ceil. Beta cell apoptosis can be induced by IL-1β,TNF-α/IFN-γ,and inhibited by exendin-4, L-isoform of JNK inhibitor. New target may be provided through regulating JNK signal pathway.     

c-Jun氨基末端激酶信号转导途径与胰岛β细胞凋亡

c-Jun N-terminal kinases (JNK) is one of the important members of mitogen activated protein kinase family. JNK pathway participates in the apoptosis of pancreatic beta ceil. Beta cell apoptosis can be induced by IL-1β,TNF-α/IFN-γ,and inhibited by exendin-4, L-isoform of JNK inhibitor. New target may be provided through regulating JNK signal pathway.     

c-Jun氨基末端激酶信号转导途径与胰岛β细胞凋亡

c-Jun N-terminal kinases (JNK) is one of the important members of mitogen activated protein kinase family. JNK pathway participates in the apoptosis of pancreatic beta ceil. Beta cell apoptosis can be induced by IL-1β,TNF-α/IFN-γ,and inhibited by exendin-4, L-isoform of JNK inhibitor. New target may be provided through regulating JNK signal pathway.     

c-Jun氨基末端激酶信号转导途径与胰岛β细胞凋亡

c-Jun N-terminal kinases (JNK) is one of the important members of mitogen activated protein kinase family. JNK pathway participates in the apoptosis of pancreatic beta ceil. Beta cell apoptosis can be induced by IL-1β,TNF-α/IFN-γ,and inhibited by exendin-4, L-isoform of JNK inhibitor. New target may be provided through regulating JNK signal pathway.     

c-Jun氨基末端激酶信号转导途径与胰岛β细胞凋亡

c-Jun N-terminal kinases (JNK) is one of the important members of mitogen activated protein kinase family. JNK pathway participates in the apoptosis of pancreatic beta ceil. Beta cell apoptosis can be induced by IL-1β,TNF-α/IFN-γ,and inhibited by exendin-4, L-isoform of JNK inhibitor. New target may be provided through regulating JNK signal pathway.     

c-Jun氨基末端激酶信号转导途径与胰岛β细胞凋亡

c-Jun N-terminal kinases (JNK) is one of the important members of mitogen activated protein kinase family. JNK pathway participates in the apoptosis of pancreatic beta ceil. Beta cell apoptosis can be induced by IL-1β,TNF-α/IFN-γ,and inhibited by exendin-4, L-isoform of JNK inhibitor. New target may be provided through regulating JNK signal pathway.     

S-adenosyl-methionine decreases ethanol-induced apoptosis in primary hepatocyte cultures by a c-Jun N-terminal kinase activity-independent mechanism

AIM:To determine the role of c-Jun N-terminal kinase(JNK)activity in ethanol-induced apoptosis and themodulation of this signaling cascade by S-Adenosyl-methionine(AdoMet).METHODS:Primary hepatocyte cultures werepretreated with 100 μmol/L SP600125,a selective JNKinhibitor,1 mL/L DMSO or 4 mmol/L AdoMet and thenexposed to 100 mmo/L ethanol.Hepatocyte apoptosiswas determined by the TUNEL and DNA ladder assays.JNK activity and its inhibition by SP600125 and AdoMetwere determined by Western blot analysis of c-junphosphorylation and Bid fragmentation.SP600125 andAdoMet effects on the apoptotic signaling pathway weredetermined by Western blot analysis of cytochrome crelease and pro-caspase 3 fragmentation.The AdoMeteffect on glutathione levels was measured by Ellman'smethod and reactive oxygen species(ROS)generationby cell cytometry.RESULTS:The exposure of hepatocytes to ethanolinduced JNK activation,c-jun phosphorylation,Bidfragmentation,cytochrome c release and pro-caspase 3cleavage;these effects were diminished by SP600125,and caused a significant decrease in ethanol-inducedapoptosis(P<0.05).AdoMet exerted an antioxidanteffect maintaining glutathione levels and decreasing ROSgeneration,without a significant effect on JNK activity,and prevented cytochrome c release and pro-caspase 3cleavage. CONCLUSION:The JNK signaling cascade is a keycomponent of the proapoptotic signaling pathwayinduced by ethanol.JNK activation may be independentfrom ROS generation,since AdoMet which exertedantioxidant properties did not have a significant effect onJNK activity.JNK pathway modulator agents and AdoMetmay be components of promising therapies for alcoholicliver disease(ALD)treatment.     

Mitogen-activated protein kinase signal transduction pathway and islet β cell apoptosis

The mitogen-activated protein kinase(MAPK)is one of the four signal system of transduction extracellular signals to cell in eukaryotic cells,including extracellular signal-regulated kinase (ERK),c-Jun NH2-terminal kinase(JNK),p38MAPK and ERK5,which participate in the cell pmlffem-tion,differentiation,transformation and apoptosis.Islet β cell apoptosis plays an important role in the pathophysiology of diabetes.Various cytokines and stress stimuli can induce β-cell apoptosis through one or more MAPK signal transduetion pathway.Investigation of MAPK signal transduetion pathway in islet β-cell apoptosis may provide new fundamental information for the prevention and treatment of diabetes.     

Tumor necrosis factor-α mediates JNK activation response to intestinal ischemia-reperfusion injury

AIM:To investigate whether tumor necrosis factor-α(TNF-α)mediates ischemia-reperfusion(I/R)-induced intestinal mucosal injury through c-Jun N-terminal kinase(JNK)activation.METHODS:In this study,intestinal I/R was induced by 60-min occlusion of the superior mesenteric artery in rats followed by 60-min reperfusion,and the rats were pretreated with a TNF-α inhibitor,pentoxifylline,or the TNF-α antibody infliximab.After surgery,part of the intestine was collected for histological analysis.The mucosal layer was harvested for RNA and protein extraction,which were used for further real-time polymerase chain reaction,enzyme-linked immunosorbent assay and Western blotting analyses.The TNF-α expression,intestinal mucosal injury,cell apoptosis,activation of apoptotic protein and JNK signaling pathway were analyzed.RESULTS:I/R significantly enhanced expression of mucosal TNF-α at both the mRNA and protein levels,induced severe mucosal injury and cell apoptosis,activated caspase-9/caspase-3,and activated the JNK signaling pathway.Pretreatment with pentoxifylline markedly downregulated TNF-α at both the mRNA and protein levels,whereas infliximab pretreatment did not affect the expression of TNF-α induced by I/R.However,pretreatment with pentoxifylline or infliximab dramatically suppressed I/R-induced mucosal injury and cell apoptosis and significantly inhibited the activation of caspase-9/3 and JNK signaling.CONCLUSION:The results indicate there was a TNFα-mediated JNK activation response to intestinal I/R injury.