protein content of cells. When lysed cells were diluted and analysed in a dot blot we found selleckbio that SH SY5Y cells treated with IFN had higher levels of cPLA2 than did untreated cells. However, pre treatment with IFN did not affect the levels of PLC 1 indicating that IFN up regulates specific pathways in these neurons. We ne t determined if pre treatment with cytokines affected prostaglandin produc tion. Levels of prostaglandin E2 were not altered by any of the cytokines tested. Prostaglandin E2 levels were signifi cantly raised after the addition of either amyloid 1 42 or HuPrP82 146, but not after the addition of control pep tides. Pre treatment of neurons of 100 pg ml IFN resulted in increased prostaglandin E2 production following the addi tion of 10 M amyloid 1 42 or 10 M HuPrP82 146.
Pros taglandin E2 levels in neurons incubated with 10 M amyloid 1 42 or 10 M HuPrP82 146 was not affected by Inhibitors,Modulators,Libraries pre treatment with TNF , IL 1, IL 6. Discussion Reports that activated microglial cells are found in close association with damaged neurons in AD raise the possi bility Inhibitors,Modulators,Libraries that glial derived cytokines are involved in neu ropathogenesis. In the current studies the survival of either primary neuronal cultures or SH SY5Y neuroblastoma cells was not affected by incubation with high concentrations of recom binant cytokines. However, while none of the cytokines were directly neuroto ic, pre treatment with IFN significantly reduced the survival of neurons that incubated with amyloid 1 42. This effect of IFN was dose dependent and was observed at concentrations pre viously reported in the cerebral corte of APP trans genic mice.
Pre treatment with IFN also increased the sensitivity Inhibitors,Modulators,Libraries of neurons to HuPrP82 146, a neuroto ic peptide found in prion diseases. However, neurons pre treated with IFN did not demonstrate increased sensitivity to all neu roto ins there was no change in the neuroto icity of stau rosporine, a drug that causes programmed cell death in neurons via activation of the ceramide pathway, or of hydrogen pero ide which causes o idation of cellular membranes. These observations strengthen the hypothe sis that IFN treatment selectively increases the e pres sion of proteins involved in specific Inhibitors,Modulators,Libraries apoptotic pathways. Previous reports showed that amyloid peptides activate PLA2, that PLA2 inhibitors protect against the amy loid 1 42 induced neuroto icity, and more specifi cally, that the cPLA2 isoform is Brefeldin_A required for induced neuroto icity.
The current study showed that IFN increased e pression of cPLA2 in neurons, a result consist ent with previous observations that IFN increases gene e pression of cPLA2 in epithelial cells. The activation of cPLA2 results in the release of arachidonic acid which is subsequently metabolised by the Leukemia CO s to prostaglandins and in the present study the increased e pression of cPLA2 in IFN treated neurons was associated with significantly greater amounts of prostaglandin E2 produced following the addition of amyloid 1 42 or HuPrP82 146. I
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- JNJ-26481585 HDAC inhibitor Western blot analysis for immunoblot analysis were OSU-HDAC42-treated lysed cells
- Activation of CaMKII and cPLA2 in A23187 stimulated DRG neurons s
- AZD6482 Ted lead heterotrimeric Gi-protein in these cells through the activation