Effect of hypoxia on HIF-1α and its sumoylation in Jurkat cells / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of hypoxia on sumoylation of HIF-1α, as well as transcriptional activity and protein stability of HIF-1α in Jurkat cells, and explore its effect and significance on modulating the transcriptional activity of down stream target gene.</p><p><b>METHODS</b>CoCl(2) was used as a chemical inducer to simulate the hypoxia environment. Real-time fluorescence quantitative PCR and western blot were used to evaluate transcriptional activity and protein stability of HIF-1α, levels of SUMO-1 and SENP1 protein, and gene transcripts of VEGF, mdr1, mdr3, Mcl-1 and survivin respectively.</p><p><b>RESULTS</b>After 4 h, 8 h, 16 h, 24 h and 72 h after hypoxia induction, the gene transcripts of HIF-1α were 0.79 ± 0.19, 2.65 ± 2.05, 4.19 ± 4.72, 2.77 ± 3.37, 0.09 ± 0.05 and 0.69 ± 0.55-fold (P > 0.01) of that of 0h in Jurkat cells, respectively, while the protein stability increased first, then decreased (P < 0.01). SENP-1 protein up-regulated first, then down-regulated, and the SUMO-1 protein changed in an opposite trend. Excepting for survivin gene, transcriptional activities of VEGF, mdr1, mdr3, and Mcl-1 were affected by the stability of HIF-1α protein.</p><p><b>CONCLUSION</b>Hypoxia induces changes in SENP-1 expression, which increases the stability of HIF-1α by decreasing the sumoylation of HIF-1α and affects biological process by regulating the transcriptional activities of VEGF, mdr1, mdr3 and Mcl-1 gene.</p>