Abstract
(p<0.05). Western blot analysis demonstrated elevated protein levels of HIF-1α, pIKKα/β and pNFκB under hypoxic conditions. This was associated with elevated transcripts for Ki67, TPH1, HIF-1α, IKKβ as well as HIF-1α downstream targets Glut1, IGF2 and TFF3 (p<0.05). Targeting NFκB with curcumin (1μM) demonstrated a significant inhibitory effect on pNFκB as well as HIF-1α protein levels (p<0.05) accompanied by decreased transcript levels of target genes. Conclusion: Hypoxia stimulates intestinal neuroendocrine EC cells and increases their viability. Stimulation of both the NFκB and the HIF-1α pathways induces 5-HT production, effects which can be reversed by inhibition with curcumin. As 5-HT plays a pathogenic role in inflammatory conditions, shock and hypoperfusion, targeting the EC cell and 5-HT production may be a therapeutic target.
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