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Aim To investigate the effect of p38 MAPK AS-ODNs on the expression of GLT-1 during the induction of brain ischemic tolerance induced by cerebral ischemic preconditioning (CIP).Methods Eighty healthy male Wistar rats with permanent occlusion of the bilateral vertebral arteries were randomly divided into 6 groups: ①Sham group (n=10);②CIP group (n=10);③ischemic insult (Ⅱ) group (n=10);④CIP+Ⅱ group (n=10);⑤p38 MAPK AS-ODNs+CIP+Ⅱ group (n=30);⑥p38 MAPK S-ODNs+CIP+Ⅱ group (n=10).Group ⑤ was divided into 5 nmol, 10 nmol and 15 nmol subgroups according to the dose of p38 MAPK AS-ODNs (n=10).The dose of p38 MAPK S-ODNs was 15 nmol.All the rats were sacrificed 6 h and 2 d after the sham operation or the last time of global brain ischemia reperfusion.Western blot and immunohistochemistry analysis were used for detecting the expression of p-p38 MAPK and GLT-1 protein.Results CIP moderately up-regulated the expression of p-p38 MAPK and significantly up-regulated the expression of GLT-1 protein, inhibited the excessively up-regulation of p-p38 MAPK and the down-regulation of GLT-1 induced by ischemic insult.p38 MAPK AS-ODNs significantly inhibited the up-regulation of p-p38 MAPK and GLT-1 protein in a dose-dependent manner during the induction of brain ischemic tolerance by CIP.Conclusion p38 MAPK AS-ODNs inhibit the up-regulation of GLT-1 during the induction of brain ischemic tolerance induced by CIP.
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Objective:To investigate the relation between the effects of IL 6 upon acute myeloid leukemia (AML) cells and its signal transduction mechanism Methods:Determined the effects of IL 6 on the growth of M1, R2, K562 and TF1 cells and the activation status of IL 6 induced nuclear factors (signal transducer and activator of transcription 3, STAT3 and nuclear factor IL6, NF IL6) by electrophoresis mobility shift assay (EMSA) Based upon these, blocked/reduced the activation of STAT3 or NF IL6 in M1 leukemia cells with STAT3/NF IL6 anti sense oligonucleotides (AS ODNs) and determined the oligonucleotides' effects upon IL 6 induced growth arrest of M1 cells Results:NF IL6 was constitutively activated in all these AML cells, while STAT3 was constitutively activated only in R2 and K562 cells Furthermore, STAT3 AS ODN reduced IL 6 induced growth arrest of M1 cells, while blocking/reducing of NF IL6 activation resulted in enhancing of IL 6 induced growth arrest Conclusion:JAK STATs pathway (especially STAT3) and Ras/MAPK pathway antagonize each other in proliferation regulation of AML cells