15 cdk1 inhibitor Cell Cycle inhibitor Myths Totally Exposed

To determine whether iNOS induction was greater in c Met null islets, we measured iNOS mRNA and protein expression, and NO formation as nitrite accumulation inside the culture media of cytokine treated PancMet KO and WT islets.

Also, a different NF kB target gene A20, a prosurvival gene in b cells, was also additional induced in PancMet KO islets compared with WT islets. Collectively, these data conrm the cdk1 inhibitor increased cytokinemediated activation of NF kB in PancMet KO islets. The addition of the NOS inhibitor L NG monomethyl Arginine or two different NF kB inhibitors, sodium salicylate, which binds to and inhibits NF kB activator IkB kinase b, or the cell permeable peptide SN 50, which inhibits the nuclear translocation of the NF kB active complex, completely blocked the increased sensitivity of PancMet KO b cells to the cytotoxic effects of cytokines. However, SN 50 did not alter STZ mediated cytotoxicity in PancMet KO b cells. Furthermore, PancMet KO and WT mouse b cells were equally sensitive to cytokines FasL cell death stimulus.

Furthermore, HGF was found to modulate specic upstream regulators of NF kB activation that are involved in cytokine mediated b cell death, signicantly decreasing the phosphorylation of inhibitor of k B a and cdk1 inhibitor increasing the phosphorylation of AKT and GSK 3b in cytokine treated human islets. HGF mediated inhibition of NF kB activation in islets was signicantly decreased by the PI3K inhibitor Wortmannin.

On the other hand, HGF protects rodent and, more important, human b cells from cytokine induced cell death.