Be changed up to 12 h after Procollagen C Proteinase doxorubicin treatment. Taken together, these results show that doxorubicin TG2 activity t erh Ht by sequential activation of DNA-Sch The reaction, ROS and calcium signaling pathways leading to persistent activation of TG2. Suppression of cell death induced by doxorubicin on previous studies TG2 activity Th have suggested that increased Hte expression of TG2 with resistance to doxorubicin is associated with. To explore the relationship between the expression of TG2 and doxorubicin resistance best term, We studied cell death in TG2 deficient MEF after doxorubicin treatment. The percentage of dead cells in TG2 deficient MEF were nearly 2-fold compared to wild-type MEF tested concentrations of doxorubicin obtained at different times Ht. Furthermore, an inverse correlation between TG activity t and cell death was observed in the MEF. As N Next is the involvement of TG2 rated efforts in the development of doxorubicin resistance.
For this purpose we generated HEK293 cells overexpressing TG2 and TG2 activitydefective a mutant in which the active site cysteine residue has been replaced by a serine residue. When cells were treated with doxorubicin, showed that TG2 293 cells approximately 5 times more intracellular Ren TG activity t, w While C277S and HEK293 293 cells showed anything similar activity Th TG. In the same experimental conditions, we compared cell death of cells and HEK293 Derived cell lines. The percentage of dead cells in TG2 293 cell line was compared to the HEK293 cell line from. In contrast, the percentage of dead cells in cell line 293 C277S Similar to the HEK293 cell line, indicating that the activity of t of TG2 transamidation essential for the cell survival in response to doxorubicin treatment. The results showed that confirmOur sequentially TG2 by signaling DNA Sch The ROS and calcium activated in cells treated with doxorubicin. This result is partly due to the nature of the cellular Ren pathway. DNA-Sch The signaling is mediated by protein phosphorylation more direct mediator.
The phosphorylation of p53, which is a marker for DNA-Sch Is the signaling was observed in 2 h after DNA-Sch And the was generally up to 12 hours after the damage suffered. In contrast to this, the produced by doxorubicin ROS a wide range of reactions of direct oxidation of macromolecules to sp t Ver Changes in gene expression through the activation of multiple signaling pathways, including normal Ver Changes in the activity of t and Expression len of calcium canals. Tats Chlich the Erh Increase of intracellular Rem calcium after 24 48 h of doxorubicin treatment. Thus, the sequential activation of TG2 by three different mechanisms lead to a lasting effect. Protein expression of TG2 was associated with doxorubicin sensitivity. TG2 was highly Ma Doxorubicin-resistant breast and lung cancer cells, and TG2 expression, the cell survival correlated with factors such as NF B activity κ t and expression of BCL 2 and BCL xL. Although conflicting evidence has been reported on the r Of the TG2, our results from experiments with TG2 deficient MEF cells with an active site mutation get transfected.