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University of Detroit MercyAberrant inhibition of HIF-1alpha by succinate in lipopolysaccharide-induced lung injury.
Lung injury caused by lipopolysaccharide (LPS) administration can lead to acute respiratory distress syndrome, which is the most common form of acute lung injury. Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor composed of the oxygen-sensitive subunit HIF-1alpha and the constitutively expressed subunit HIF-1beta. In the present study, we found that succinate, the metabolite of activated Kupffer cells, decreased HIF-1alpha protein by inhibiting the protein synthesis of HIF-1alpha. Succinate also decreased the mRNA level of HIF-1alpha in HFL-1 cells. Moreover, the protein level of HIF-1beta in the nuclei of HFL-1 cells was increased by exposure to LPS. These results indicate that HIF-1 is down-regulated by succinate through increasing the degradation of HIF-1alpha, at least in part.More information on earlier study
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