PMID- 15489637
OWN - NLM
STAT- MEDLINE
DCOM- 20050324
LR  - 20190917
IS  - 1073-2322 (Print)
IS  - 1073-2322 (Linking)
VI  - 22
IP  - 5
DP  - 2004 Nov
TI  - Butyrate suppresses hypoxia-inducible factor-1 activity in intestinal epithelial 
      cells under hypoxic conditions.
PG  - 446-52
AB  - Interaction between the products of intestinal bacteria and the intestinal 
      epithelial cells is a key event in understanding the biological, physiological, 
      and pathological functions of the intestinal epithelium. Here, we examined the 
      effect of butyrate, one of the major intestinal bacterial products, on 
      hypoxia-inducible factor-1 (HIF-1) activity under hypoxic conditions in 
      intestinal epithelial cells. HIF-1 activity was assessed by luciferase assay 
      using cytoplasmic extracts of intestinal epithelial cells, Caco-2, and IEC-6 
      cells. These cells were transiently transfected with hypoxia response element 
      (HRE)-luciferase reporter plasmids and cultured under hypoxic conditions in the 
      presence or absence of sodium butyrate (NaB). The effect of NaB on HRE DNA 
      binding activity in Caco-2 cells under hypoxic conditions was assessed by 
      electrophoretic mobility shift assay. Expression of a hypoxia-responsive gene 
      encoding intestinal trefoil factor (ITF) in Caco-2 cells after NaB treatment was 
      assessed using reverse-transcription PCR. The barrier function of Caco-2 cells 
      under hypoxic conditions was also evaluated by transepithelial electrical 
      resistance measurement. NaB suppressed up-regulation of HIF-1 transcriptional 
      activity under hypoxic conditions in Caco-2 and IEC-6 cells. In parallel, NaB 
      reduced HRE DNA binding activity under the same conditions. Furthermore, NaB 
      down-regulated enhanced transcription of ITF gene. Addition of NaB under hypoxic 
      conditions delayed recovery of transepithelial electrical resistance of the 
      monolayers after hypoxia-reoxygenation treatment. These findings indicate that 
      NaB suppresses HIF-1 transcriptional activity on hypoxia-responsive genes by 
      reducing the HRE DNA binding activity under hypoxic conditions in intestinal 
      epithelial cells.
FAU - Miki, Keita
AU  - Miki K
AD  - Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu 
      431-3192, Japan. k-miki3@mug.biglobe.ne.jp
FAU - Unno, Naoki
AU  - Unno N
FAU - Nagata, Toshi
AU  - Nagata T
FAU - Uchijima, Masato
AU  - Uchijima M
FAU - Konno, Hiroyuki
AU  - Konno H
FAU - Koide, Yukio
AU  - Koide Y
FAU - Nakamura, Satoshi
AU  - Nakamura S
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Butyrates)
RN  - 0 (Fatty Acids)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Mucins)
RN  - 0 (Muscle Proteins)
RN  - 0 (Peptides)
RN  - 0 (Transcription Factors)
RN  - 0 (Trefoil Factor-2)
RN  - 7G33012534 (Sodium Oxybate)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Butyrates/*pharmacology
MH  - Caco-2 Cells
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Down-Regulation
MH  - Electrophysiology
MH  - Epithelial Cells/drug effects/*metabolism
MH  - Fatty Acids/chemistry
MH  - Humans
MH  - *Hypoxia
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Intestinal Mucosa/*metabolism
MH  - Intestines/drug effects
MH  - Luciferases/metabolism
MH  - Mucins/metabolism
MH  - Muscle Proteins/metabolism
MH  - Peptides/metabolism
MH  - Plasmids/metabolism
MH  - Rats
MH  - Response Elements
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sodium Oxybate/pharmacology
MH  - Time Factors
MH  - Transcription Factors/*metabolism
MH  - Transfection
MH  - Trefoil Factor-2
MH  - Up-Regulation
EDAT- 2004/10/19 09:00
MHDA- 2005/03/25 09:00
CRDT- 2004/10/19 09:00
PHST- 2004/10/19 09:00 [pubmed]
PHST- 2005/03/25 09:00 [medline]
PHST- 2004/10/19 09:00 [entrez]
AID - 00024382-200411000-00008 [pii]
AID - 10.1097/01.shk.0000140664.80530.bd [doi]
PST - ppublish
SO  - Shock. 2004 Nov;22(5):446-52. doi: 10.1097/01.shk.0000140664.80530.bd.