Uction in a HIF protein levels and Transaktivierungsaktivit t, as Topotecan shown by a completely Requests reference requests getting inhibition of the activation of luciferase reporter gene under the control demonstrated HRE consensus, in contrast to cells transfected with empty plasmid of contr on. In line with the results obtained with the dominant negative DARNT abolished knockdown of HIF-1 is the protection of dexrazoxane weight Leads, may need during the transfection of a vector, a non-tape shGFP effective sequence had no significant effect. To further demonstrate that HIF-1 is important for the protective effect of dexrazoxane, we investigated whether HIF-1 activation also provides cardioprotection to doxorubicin in cells not exposed to iron chelation. Transfection with an expression vector encoding HIF 1a entered Born with a high degree of HIF-proteins strongly stimulated a strong and HRE-dependent Independent transcription and led to significant cell protection LDE225 against cell death and apoptosis doxorubicinmediated as revealed by MTT and caspase-3 trials.
These experiments showed that overexpression of HIF 1a H9c2 cardiomyocytes from doxorubicin-induced toxicity T in the absence of protection by dexrazoxane. Effect of chloroxine dexrazoxane on the expression of HIF-target genes in H9c2 cells to further investigate the Transkriptionsaktivit t of HIF-function observed in cells activated dexrazoxane, we studied its expression of endogenous genes under the control of the transcription of HIF in cells exposed to dexrazoxane and doxorubicin. The immunoblots in Figure 7A show that the levels of aldolase A, a typical target gene of HIF increased more Ht after dexrazoxane doxorubicin treatment as planned and returned to contr L level in cells transfected with DARNT. Having shown that dexrazoxane prevents apoptosis, we investigated whether HIF-target genes that may play a r There at the F Promotion cell survival after doxorubicin-mediated damage in H9c2 cells treated dexrazoxane were induced. Immunoblot analysis showed that increased the Androgen Receptor Antagonists doxorubicin plus dexrazoxane Hte anti-apoptotic proteins MCL1 is doxorubicin does not inhibit the expression of HIF and transactivation capacity t.
Immunoblot analysis of nuclear extracts from untreated H9c2 cells and cells for 24 h with doxorubicin, dexrazoxane exposed for 3 h alone or pretreated with DRZ for 3 h and then exposed to DOX, 1a with the anti-HIF Antique Body. Blots were incubated with antibodies Rpern against TFIID as probed contr The load. The panel shows a repr Resentative blot and densitometric quantification relative to the amount values C Relative luciferase activity Transfected T cells in fa H9c2 is transiently transfected with a construct was monitored in the luciferase There are a HRE multimer and treated as described for panel A. The cells were co-use of a vector, which controls the gene The Renilla luciferase. Luciferase activity was t determined after 24 hours, corrected for transfection efficiency to Renilla luciferase activity t recorded on the activity and normalized to t in untreated cells. The mean values SD. P 0.001, P 0.01, P 0.05, N 3 HIF, hypoxia inducible factor, TFIID, transcription factor IID to treat the clinical use of anthracyclines in many human tumors is characterized by its Kardiotoxizit Tt Dliche dose related, which was attributed to limited.