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Gliomas are highly invasive brain tumors with the occurence of numerous microglial cells arround the tumor. The density of these cells positively correlates with the malignancy, invasiveness and grading of gliomas. Sialic acid-binding immunoglobulin superfamily lectins (Siglecs) are members of immunoglobulin superfamily that recognize sialic acid residues of glycoproteins. Siglecs have intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIM), implicating them in the suppression of immunoreceptor signaling. Siglec-F is a CD33-related Siglec that binds to 2.3-, 2.6- and weakly 2.8-linked sialic acid. We analysed distribution and function of sialic acids and their receptor, Siglec-F, in glioma-microglia interactions. We observed Siglec-F gene transcription and Siglec-F protein expression in cultured embryonic stem cells derived microglia as well as high level of sialic acids in the mouse glioma cell line GL261. Flow cytomety analysis showed that sialylated structures expressed at the plasma membrane of glioma cells are recognized by recombinant mouse Siglec-F/Fc chimera. Enzymatic desialylation of the glioma cells with endoneuraminidase and α-neuraminidase significantly decreased binding of Siglec-F protein. Our data demonstrate that activation of immunosuppressive Siglec-F receptor by sialic acids can modulate microglia activity and immune response against malignant cells.
Propofol can be potentially beneficial in oxidative stress related malignancies as neurodegenerative diseases and traumatic brain injury but its signalling pathways are poorly understood. In this study effect of propofol on astroglial signalling in oxidative stress was evaluated. Ten days old cultures of rat astroglial cells were treated for 1 hour with t-butyl hydroperoxide (tBHP) to induce oxidative stress following by 1 hour propofol. We measured cytotoxicity, changes in cell growth and apoptosis as well as alterations in expression and acetylation of chromatin core H3 and H4 histone proteins and changes in native and phosphorylated cAMP-response-element-binding protein (CREB). tBHP induced limited cytotoxicity, increased apoptosis, decreased glutamine synthetase and enolase activities, decreased nuclear CREB, CREB-P and histone proteins but unchanged cytosolic CREB and histone acetyltransferase (HDAC) expression. Propofol clearly protected the cells against tBPH-induced toxicity, normalized alterations in cell growth, restored to some extent glial enzyme activities and reduced apoptotic cell numbers. Also, propofol restored H3 but not H4 expression/activation, but was without effect on decreased nuclear CREB expression/activation. These data show that oxidative stress in cultured astroglia significantly affects nuclear CREB and histone proteins and point to the protective role of propofol.
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