PMID- 7644539
OWN - NLM
STAT- MEDLINE
DCOM- 19950921
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 92
IP  - 17
DP  - 1995 Aug 15
TI  - The cis-acting phorbol ester "12-O-tetradecanoylphorbol 13-acetate"-responsive 
      element is involved in shear stress-induced monocyte chemotactic protein 1 gene 
      expression.
PG  - 8069-73
AB  - Vascular endothelial cells, serving as a barrier between vessel and blood, are 
      exposed to shear stress in the body. Although endothelial responses to shear 
      stress are important in physiological adaption to the hemodynamic environments, 
      they can also contribute to pathological conditions--e.g., in atherosclerosis and 
      reperfusion injury. We have previously shown that shear stress mediates a 
      biphasic response of monocyte chemotactic protein 1 (MCP-1) gene expression in 
      vascular endothelial cells and that the regulation is at the transcriptional 
      level. These observations led us to functionally analyze the 550-bp promoter 
      region of the MCP-1-encoding gene to define the cis element responding to shear 
      stress. The shear stress/luciferase assay on the deletion constructs revealed 
      that a 38-bp segment (-53 to -90 bp relative to the transcription initiation 
      site) containing two divergent phorbol ester "12-O-tetradecanoylphorbol 
      13-acetate" (TPA)-responsive elements (TRE) is critical for shear inducibility. 
      Site-specific mutations on these two sites further demonstrated that the proximal 
      one (TGACTCC) but not the distal one (TCACTCA) was shear-responsive. Shear 
      inducibility was lost after the mutation or deletion of the proximal site. This 
      molecular mechanism of shear inducibility of the MCP-1 gene was functional in 
      both the epithelial-like HeLa cells and bovine aortic endothelial cells (BAEC). 
      In a construct with four copies of the TRE consensus sequences TGACTACA followed 
      by the rat prolactin minimal promoter and luciferase gene, shear stress induced 
      the reporter activities by 35-fold and 7-fold in HeLa cells and BAEC, 
      respectively. The application of shear stress on BAEC also induced a rapid and 
      transient phosphorylation of mitogen-activated protein kinases. Pretreatment of 
      BAEC with TPA attenuated the shear-induced mitogen-activated protein kinase 
      phosphorylation, suggesting that shear stress and TPA share a similar signal 
      transduction pathway in activating cells. The present study provides a molecular 
      basis for the transient induction of MCP-1 gene by shear stress.
FAU - Shyy, J Y
AU  - Shyy JY
AD  - Department of Bioengineering, University of California, San Diego, La Jolla 
      92093-0412, USA.
FAU - Lin, M C
AU  - Lin MC
FAU - Han, J
AU  - Han J
FAU - Lu, Y
AU  - Lu Y
FAU - Petrime, M
AU  - Petrime M
FAU - Chien, S
AU  - Chien S
LA  - eng
GR  - HL 19454/HL/NHLBI NIH HHS/United States
GR  - HL 43026/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Cytokines)
RN  - 0 (DNA Primers)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Animals
MH  - Aorta
MH  - Base Sequence
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cattle
MH  - Cells, Cultured
MH  - Chemokine CCL2
MH  - Chemotactic Factors/*biosynthesis/genetics
MH  - Consensus Sequence
MH  - Cytokines/biosynthesis
MH  - DNA Primers
MH  - Endothelium, Vascular/metabolism/*physiology
MH  - Epithelium/physiology
MH  - *Gene Expression
MH  - HeLa Cells
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Polymerase Chain Reaction
MH  - Promoter Regions, Genetic
MH  - *Regulatory Sequences, Nucleic Acid
MH  - Restriction Mapping
MH  - *Stress, Mechanical
MH  - Tetradecanoylphorbol Acetate/*pharmacology
MH  - Transcription, Genetic
MH  - Transfection
PMC - PMC41288
EDAT- 1995/08/15 00:00
MHDA- 1995/08/15 00:01
PMCR- 1996/02/15
CRDT- 1995/08/15 00:00
PHST- 1995/08/15 00:00 [pubmed]
PHST- 1995/08/15 00:01 [medline]
PHST- 1995/08/15 00:00 [entrez]
PHST- 1996/02/15 00:00 [pmc-release]
AID - 10.1073/pnas.92.17.8069 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8069-73. doi: 
      10.1073/pnas.92.17.8069.