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IL-1 β alone

Inhibition of HIF signal transduction A) Inhibition of HRE-HIF-1 α DNA binding. Dose-dependent down-regulation of hypoxia-induced gene transactivation (BNIP3 mRNA) by B) AW 464 C) AJM 290 and D) protein (CA-IX, BNIP3) expression. D. A.

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IL-1 β alone

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  1. Inhibition of HIF signal transduction A) Inhibition of HRE-HIF-1α DNA binding. Dose-dependent down-regulation of hypoxia-induced gene transactivation (BNIP3 mRNA) by B) AW 464 C) AJM 290 and D) protein (CA-IX, BNIP3) expression. D A 1. Cos 7/CoCl2 2. MDA 468 Nx 3. MDA 468 Hx 4. MDA 468 Hx 10 μM AJM 290 5. MDA 468 Hx 10 μM AW 464 6. Cos 7/CoCl2 + 500 ng cmpt oligo 7. MDA 468 + 500 ng cmpt oligo. IL-1β alone B PMX 464 + IL-1β C E F RCC4 + VHL N Hypoxia AJM290 AW464 C C 1 2.5 10 1 2.5 10 μM Normoxia Hypoxia C 1.0 2.5 10 C 1.0 2.5 10 μM AJM 290 AW 464 BNIP3 CA-IX Inhibition of NFkB activation Inhibition of A) IK kinase activity C) IKB phosphorylation D) nuclear translocation E) DNA binding and F) NFkB-activated transcription. A A C B D .

  2. whole cell lysates IP: Trx  p54  p54 phospho-JNK  p46  p46  ASK-1 total JNK  Trx DMSO 1 DMSO 1 DMSO 2 DMSO 2 5mM AJM 290 5mM AJM 290 5mM AW 464 5mM AW 464 actin DMSO 0.5 1 5 10 0 5 30 60 180 180 min DMSO 3h AW 464 (mM) AW 464 (5mM) AW 464 induced ASK-1/Trx dissociation and JNK activation in HCT116 cells.

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