Hypoxic up-regulation of erythroid 5-aminolevulinate synthase.

摘要: The erythroid-specific isoform of 5-aminolevulinate synthase (ALAS2) catalyzes the rate-limiting step in heme biosynthesis. hypoxia-inducible factor-1 (HIF-1) transcriptionally up-regulates erythropoietin, transferrin, and transferrin receptor, leading to increased erythropoiesis hematopoietic iron supply. To test hypothesis that ALAS2 expression might be regulated by a similar mechanism, we exposed murine erythroleukemia cells hypoxia (1% O(2)) found an up 3-fold up-regulation mRNA levels increase cellular content. A fragment promoter ranging from -716 +1 conveyed responsiveness heterologous luciferase reporter gene construct transiently transfected HeLa cells. In contrast, depletion, known induce HIF-1 activity but inhibit translation, did not activity. Mutation previously predicted HIF-1-binding site (-323/-318) within this DNA-binding assays revealed hypoxic is independent putative site.