Indirect evi dence for the participation of DAF in apoptotic events has been demonstrated in malignant tumors and neutrophils. In this study, DAF treated cells showed an attenuated level of neuronal cell click here apoptosis induced by the hypoxic ischemic insult. We observed that cultured rat neurons constitutively possessed C3 protein which is consistent with recent findings demonstrating that C3 was present in mouse neurons. In previous studies from our laboratory, DAF was shown to inhibit formation of MAC in murine mesenteric I R models and unpublished data as well as sup press production of C3a and MAC in rodent and porcine hemorrhagic shock. Of particular interest is our observation that treatment with DAF sig nificantly reduced the increase in C3 expression Inhibitors,Modulators,Libraries as well as C3a and MAC Inhibitors,Modulators,Libraries formation Inhibitors,Modulators,Libraries in hypoxic neuronal cells.
In addition to the well described regulatory Inhibitors,Modulators,Libraries function of DAF on complement activation, it has become increasingly apparent that this molecule might also act as a signal transducing molecule. DAF has been found to associate with Src protein tyrosine kinases such as p56lck and p59fyn in human T cells. There is strong evi sion and neurosurgical procedure. In the present study, we demonstrate that DAF treatment significantly decreases the activation of c Src during ischemia like conditions. Although the mechanism by which DAF reg ulates activation of Src kinase is unknown, there is increasing evidence that Src family kinases act as a point of convergence for various signaling pathway, including the pathway that signals via G coupled receptors.
Thus, it is possible that the inhibition of c Src activity by DAF could be via a direct association of DAF and c Src. Neurons have been identified as the principal CNS cell that prominently expresses the C3a receptor under physi ological conditions. Significant up regulation Inhibitors,Modulators,Libraries of C3aR in murine brain after cerebral ischemia has been observed. We found that DAF dramatically dimin ished neuronal C3aR induced by the hypoxic ischemic conditions. C3aR specifically binds with high affinity to C3a and high affinity binding sites are abundantly expressed on cultured human astrocytes. The finding that increased C3aR was present in hypoxic cultured neurons and was associ ated with C3a is quite important since this can explain why soluble C3a was detected in the cell lysates.
C3a C3aR interaction was markedly reduced in the presence of DAF by limiting expression of C3aR and C3a. C3aR is a G protein coupled receptor which initiates intracellular signaling when C3a binds to it. Our findings sug gest that autocrine intracrine www.selleckchem.com/products/Imatinib-Mesylate.html C3a might be involved in the regulation of neuronal functions via binding to C3aR and subsequent C3a C3aR engagement which implies a key link to the down stream Src and caspase signals.