The resistance to doxorubicin in breast cancer cells and posaconazole Noxafil suggest that anything similar mechanisms can k In tumor cells and cardiomyocytes to be in operation. HIF HIF 1a and 2a have different tissue distributions, but are connected by common stimuli and share many target genes and functions, preventing any clear determination enabled her r The specific. We demonstrated that both isoforms of HIF that are sensitive to degradation Similar to the von Hippel Lindaumediated ubiquitin-proteasome-dependent are you Ngig were induced by dexrazoxane, but we k Can not determine the contribution is for the protection of H9c2 cells. Shall, however, suggests the loss of cardioprotection in cells with shRNA-mediated pkc delta inhibitor inhibition of HIF 1a and specific resistance to doxorubicin toxicity t in cells overexpressing HIF 1a that this isoform plays a role Important role. Doxorubicin inhibits HIF-1 transcriptional activity strongly t in tumor cells, but another study found no inhibitory effect.
We observed that the partial inhibition of the transactivation ability F Of HIF in the doxorubicin treated H9c2 cells, and not enough to prevent its protective function. In particular, we have shown that the expression of HIF-target genes not affected by doxorubicin and was also in H9c2 cells exposed to dexrazoxane plus doxorubicin regulated. The different experimental conditions and different cell types explained Ren the discrepancy. We also assessed the effects of dexrazoxane on the expression of several HIF-target Fesoterodine genes in H9c2 cells and found that it is the expression of the target gene of HIF typical aldolase A, an enzyme of glycolysis that loan St a positive effect on cell function and the adaptation to hypoxia. In line with the r The anti-apoptotic genes regulated HIF and preventing apoptosis induced by pretreatment with dexrazoxane, we observed strong up regulation of survivin and MCL1, which are both members of the family of inhibitors of apoptosis proteins. Our results are consistent with the essential function of survivin in cell division and inhibition of apoptosis is known, and with the recent demonstration that the overexpression of survivin in cardiomyocytes inhibited apoptosis induced by doxorubicin. In addition, it was shown that MCL1 with the Lebensf Associated ability of cardiac muscle cells. Our previous results showed that doxorubicin cardiomyocyte apoptosis by inhibiting the antiapoptotic HO 1, which facilitate a HIF target gene.
consistent with these results, exposure to dexrazoxane capable of inhibiting HO-1 expression was exerted by doxorubicin and neutralize come Born a strong increase in HO-1 levels. We recall that in our study, the inhibition of HIF-activity t by the expression of cell death induced by position doxorubicin DARNT prevents and suppresses the induction of these antiapoptotic genes, which indicates their R Induced cardioprotection in the dexrazoxane. The effect of incomplete Requests reference requests getting Inhibition of HIF-activity t is applied, can be one of the following the fact that all cells were transfected, but the inclusion of other transcription factors can not be excluded. On the other hand, we have no significant modulation of Bcl xL, an anti-apoptotic protein that protects H9c2 cardiomyocytes from apoptosis induced by doxorubicin. Our results are in flax.