PMID- 11886167
OWN - NLM
STAT- MEDLINE
DCOM- 20020709
LR  - 20211203
IS  - 1043-4666 (Print)
IS  - 1043-4666 (Linking)
VI  - 17
IP  - 1
DP  - 2002 Jan 7
TI  - Stabilization of hypoxia-inducible factor-1alpha is involved in the hypoxic 
      stimuli-induced expression of vascular endothelial growth factor in osteoblastic 
      cells.
PG  - 14-27
AB  - It has been suggested that blood vessel formation is an important event coupled 
      to bone formation. The expression of vascular endothelial growth factor (VEGF), a 
      potent angiogenic factor, has been shown to be greatly stimulated in osteoblasts 
      by hypoxic stimuli such as deprivation of oxygen and treatment with cobalt. In 
      other cell types, hypoxia-inducible factor-1 (HIF-1) that binds hypoxia-response 
      element (HRE) has been shown to mediate gene expression induced by hypoxic 
      stimuli. In this study, we investigated the effects of hypoxic stimuli on HIF-1, 
      HRE, and VEGF in osteoblastic cell lines. Exposure of these cells to hypoxia or 
      cobalt resulted in a great increase in the protein level of HIF-1alpha and the 
      gene expression of VEGF. Transforming growth factor-beta1, prostaglandin E2, 
      dexamethasone, and 1,25-dihydroxyvitamin D3 that have been shown to regulate VEGF 
      gene expression in osteoblasts had no effect on HIF-1alpha induction. Blocking 
      the enzymatic activity of phosphatidylinositol 3-kinase, p38, MEK-1 did not have 
      any effect on the cobalt-stimulated increase of HIF-1alpha in these cells. In 
      contrast, N-acetylcysteine (NAC), a scavenger of reactive oxygen species, 
      abolished the cobalt induction of HIF-1alpha and that of the VEGF and a 
      HRE-driven reporter genes. However, the hypoxia responses were not affected by 
      NAC. These findings suggest that hypoxia and cobalt can induce VEGF gene 
      expression in osteoblasts by increasing the level of HIF-1alpha protein through 
      different mechanisms.
CI  - Copyright 2002 Elsevier Science Ltd.
FAU - Kim, Hong-Hee
AU  - Kim HH
AD  - National Research Laboratory for Bone Metabolism, Chosun University, Kwangju, 
      Korea.
FAU - Lee, Shee Eun
AU  - Lee SE
FAU - Chung, Woon Jae
AU  - Chung WJ
FAU - Choi, Youngyeon
AU  - Choi Y
FAU - Kwack, KyuBum
AU  - Kwack K
FAU - Kim, Si Wouk
AU  - Kim SW
FAU - Kim, Myong Soo
AU  - Kim MS
FAU - Park, Hyunsung
AU  - Park H
FAU - Lee, Zang Hee
AU  - Lee ZH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Glucocorticoids)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lymphokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 3G0H8C9362 (Cobalt)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (MAP3K1 protein, human)
RN  - FXC9231JVH (Calcitriol)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/chemistry
MH  - Blotting, Western
MH  - Calcitriol/pharmacology
MH  - Cell Line
MH  - Cobalt/pharmacology
MH  - Dexamethasone/pharmacology
MH  - Dinoprostone/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Growth Factors/*biosynthesis/chemistry
MH  - Free Radical Scavengers/pharmacology
MH  - Gene Expression
MH  - Glucocorticoids/pharmacology
MH  - Humans
MH  - Hypoxia
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Luciferases/metabolism
MH  - Lymphokines/*biosynthesis/chemistry
MH  - *MAP Kinase Kinase Kinase 1
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Osteoblasts/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - RNA, Messenger/metabolism
MH  - Reactive Oxygen Species
MH  - Response Elements
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Transcription Factors/*chemistry/*metabolism
MH  - Transfection
MH  - Transforming Growth Factor beta/pharmacology
MH  - Transforming Growth Factor beta1
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2002/03/12 10:00
MHDA- 2002/07/10 10:01
CRDT- 2002/03/12 10:00
PHST- 2002/03/12 10:00 [pubmed]
PHST- 2002/07/10 10:01 [medline]
PHST- 2002/03/12 10:00 [entrez]
AID - S1043466601909858 [pii]
AID - 10.1006/cyto.2001.0985 [doi]
PST - ppublish
SO  - Cytokine. 2002 Jan 7;17(1):14-27. doi: 10.1006/cyto.2001.0985.