期刊
BIOCHEMICAL JOURNAL
卷 412, 期 -, 页码 477-484出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20080476
关键词
hypoxia; hypoxia-inducible factor 1 (HIF-1); nuclear factor kappa B (NF-kappa B); tumour necrosis factor (TNF)
资金
- Biotechnology and Biological Sciences Research Council Funding Source: Medline
- Medical Research Council [G0601098] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- MRC [G0601098] Funding Source: UKRI
- Medical Research Council [G0601098] Funding Source: researchfish
HIF (hypoxia-inducible factor) is the main transcription factor activated by low oxygen tensions. HIF-1 alpha (and other a subunits) is tightly controlled mostly at the protein level, through the concerted action of a class of enzymes called PHDs (prolyl hydroxylases) 1, 2 and 3. Most of the knowledge of HIF derives from studies following hypoxic stress; however, HIF-1 alpha stabilization is also found in non-hypoxic conditions through an unknown mechanism. In the present study, we demonstrate that NF-kappa B (nuclear factor kappa B) is a direct modulator of HIF-1 alpha expression. The HIF-1 alpha promoter is responsive to selective NF-kappa B subunits. siRNA (small interfering RNA) studies for individual NF-kappa B members revealed differential effects on HIF-1 alpha mRNA levels, indicating that NF-kappa B can regulate basal HIF-1 alpha expression. Finally, when endogenous NF-kappa B is induced by TNF alpha (tumour necrosis factor alpha) treatment, HIF-1 alpha levels also change in an NF-kappa B-dependent manner. In conclusion, we find that NF-kappa B can regulate basal TNF alpha and, in certain circumstances, the hypoxia-induced HIF-1 alpha.
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