PMID- 9027739 OWN - NLM STAT- MEDLINE DCOM- 19970519 LR - 20190725 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 51 IP - 2 DP - 1997 Feb TI - Hypoxia-inducible factor-1 alpha is regulated at the post-mRNA level. PG - 560-3 AB - The hypoxia-inducible factor-1 (HIF-1) is involved in the induction of oxygen regulated genes such as erythropoietin and vascular endothelial growth factor (VEGF). HIF-1 is a heterodimeric transcription factor consisting of an alpha and a beta subunit. The question of how HIF-1 itself is regulated remains to be elucidated. Studies performed in human Hep3B hepatoma cells suggested that the prevalent mode of HIF-1 action is an increase in HIF-1 alpha steady-state mRNA and protein levels after hypoxic exposure. In contrast to the reported very low basal HIF-1 alpha mRNA levels, however, we detected HIF-1 alpha mRNA in several cell lines cultured under normoxic conditions, although no HIF-1 DNA binding activity was observed. Following hypoxic induction, VEGF mRNA levels and HIF-1 DNA binding activity increased, but HIF-1 alpha mRNA levels remained largely unchanged. One possible explanation for this discrepancy might be that HIF-1 DNA binding activity does not follow HIF-1 alpha mRNA kinetics. We therefore incubated HeLaS3 cells in tonometers for 7.5 minutes up to four hours at either 20% O2 or 0.5% O2. Although there was some variation in HIF-1 alpha mRNA levels, we did not find significant changes over this time frame, suggesting that HIF-1 alpha is not transcriptionally regulated. FAU - Wenger, R H AU - Wenger RH AD - Institute of Physiology, University of Zurich-Irchel, Switzerland. FAU - Kvietikova, I AU - Kvietikova I FAU - Rolfs, A AU - Rolfs A FAU - Gassmann, M AU - Gassmann M FAU - Marti, H H AU - Marti HH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (DNA-Binding Proteins) RN - 0 (Endothelial Growth Factors) RN - 0 (HIF1A protein, human) RN - 0 (Hif1a protein, mouse) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Lymphokines) RN - 0 (Nuclear Proteins) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Vascular Endothelial Growth Factors) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Cell Hypoxia/genetics/physiology MH - Cell Line MH - DNA/metabolism MH - DNA-Binding Proteins/chemistry/*genetics/*metabolism MH - Endothelial Growth Factors/genetics MH - Humans MH - Hypoxia-Inducible Factor 1 MH - Hypoxia-Inducible Factor 1, alpha Subunit MH - Kinetics MH - Lymphokines/genetics MH - Mice MH - Nuclear Proteins/chemistry/*genetics/*metabolism MH - RNA Processing, Post-Transcriptional MH - RNA, Messenger/*genetics/metabolism MH - *Transcription Factors MH - Vascular Endothelial Growth Factor A MH - Vascular Endothelial Growth Factors EDAT- 1997/02/01 00:00 MHDA- 1997/02/01 00:01 CRDT- 1997/02/01 00:00 PHST- 1997/02/01 00:00 [pubmed] PHST- 1997/02/01 00:01 [medline] PHST- 1997/02/01 00:00 [entrez] AID - S0085-2538(15)59919-5 [pii] AID - 10.1038/ki.1997.79 [doi] PST - ppublish SO - Kidney Int. 1997 Feb;51(2):560-3. doi: 10.1038/ki.1997.79.