Sed as Ma for druginduced Sch and displays the necrotic Tyrphostin AG-1478 cell death. We then examined whether exposure to dexrazoxane concentration sufficient to activate HIF was ameliorates cell death in H9c2 cardiomyocytes with 0.5 mM doxorubicin treated. 2A shows that cells pretreated with 10 mM dexrazoxane were significantly protected, 77% were alive after exposure compared to doxorubicin. In accordance with previous results showing that apoptosis is the h Most common form of cell death in H9c2 cells that low doses of doxorubicin was the activity of t of caspase 3 twice as high as in cells not observed with 0.5 and mMdoxorubicin returned to control values in cells preincubated with dexrazoxane. Dexrazoxane pre-treatment, the Erh Increase the doxorubicin-induced cell death by apoptosis by measuring Annexin V binds to phosphatidylserine externalization assessed counteracted. Since the mitochondria-mediated pathway of apoptosis is important in apoptosis induced by doxorubicin, also Adriamycin measured release of cytochrome c and found that it was improved to 0.5 mM and doxorubicin was prevented by dexrazoxane pretreatment. The exposure to dexrazoxane alone had no significant influence apoptosis.
The protective effect of dexrazoxane dependent Ngig HIF-1 activity to investigate t To the r Of HIF-1 in cardioprotection dexrazoxanemediated directly, we examined Opioid Receptor the F Ability to prevent toxicity of dexrazoxane to t of doxorubicin in H9c2 cells lacking HIF-1 activity t. First, we conducted a controlled experiment To determine whether the induction of HIF-1 Transkriptionsaktivit t in cells that dexrazoxane was suspended in cells that dexrazoxane exposed plus doxorubicin doxorubicin are held as, thus affecting gene expression in muscle and an HIF ABH- Independent transcriptional activity T, k can blunt HIF-1 activation and thus the protective effect of iron chelation. Shows, however, 3A indicates that the protein HIF 1a Similar in cells that were exposed to dexrazoxane, and those exposed to dexrazoxane plus doxorubicin than planned. In addition, the Luciferaseaktivit went t Born of several HRE sequences was somewhat inhibited in cells exposed to dexrazoxane plus doxorubicin Clofarabine were compared to those treated with dexrazoxane alone, but was still much h Forth as in the cells not treated.
Having shown that HIF is active 1 in H9c2 cells, containing 0.5 mM doxorubicin, we examined the Lebensf Ability of the cells in H9c2 cells with dominant negative HIF DARNT 1b subunit transfected and exposed to doxorubicin with or without pretreatment dexrazoxane. MTT assays showed that the protective effect of dexrazoxane lost in transfected cells, that the mortality t not significantly h Ago than in cells amount without pretreatment dexrazoxane doxorubicin, indicating that HIF plays a role The dexrazoxanemediated in protecting H9c2 cells. Likewise, a protective effect of dexrazoxane was caspase 3 activity t was measured to see the effect on apoptosis. To further verify the r The HIF-1 in the protection of dexrazoxane doxorubicin pretreated H9c2 cells, we used shRNA technology to specifically supplement HIF 1a. The efficient transfection of H9c2 cells encoded with a set of four expression vectors leads shRNA against HIF 1a to a red.