PMID- 8191411
OWN - NLM
STAT- MEDLINE
DCOM- 19940617
LR  - 20190727
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 73
IP  - 3-4
DP  - 1994 Feb 15
TI  - Up-regulation of tissue factor mRNA in human umbilical vein endothelial cells by 
      calmodulin inhibitor W7.
PG  - 177-84
AB  - Tissue factor (TF) is an integral membrane glycoprotein that serves as a cofactor 
      for the blood coagulation factor VIIa. The induction of TF synthesis and activity 
      on the surface of endothelial cell membrane is initiated by lipopolysaccharide 
      (LPS), phorbol 12-myristate 13-O-acetate (PMA), and inflammatory factors such as 
      interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha). 
      Treatment of cells with 1 micrograms/ml LPS induced an 8.7-fold increase in total 
      TF activity compared with nontreated cells. Co-incubation with 1 micrograms/ml 
      LPS and 30 microM W7, a potent calmodulin inhibitor, resulted an additional 2.0 
      fold increase in total TF activity. A similar tendency was observed after 
      treatment with either TNF alpha plus W7, or IL-1 beta plus W7. The effect of W7 
      appeared to be synergistic since incubation with 30 microM W7 alone increased TF 
      activity levels to only 1.5-fold that of control cells. Northern blot analysis 
      showed that W7 and LPS-treated endothelial cells expressed about three times 
      higher levels of TF mRNA compared to LPS-treated cells. Treatment with W7 and LPS 
      resulted in a slow but large calcium influx into endothelial cells. This result 
      suggest that the contribution of W7 may be dependent mainly on calcium influx by 
      unknown mechanisms rather than direct inhibition of calmodulin, because calcium 
      ionophore treatment also showed a synergistic effect on TF mRNA and activity 
      expression.
FAU - Wakita, K
AU  - Wakita K
AD  - Department of Molecular Biology Research Laboratory, Daiichi Pharmaceutical Co. 
      Ltd., Tokyo, Japan.
FAU - Marumoto, Y
AU  - Marumoto Y
FAU - Horiuchi, T
AU  - Horiuchi T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Calmodulin)
RN  - 0 (Endotoxins)
RN  - 0 (Interleukin-1)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sulfonamides)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 65595-90-6 (W 7)
RN  - 67924-63-4 (endotoxin, Escherichia coli)
RN  - 9035-58-9 (Thromboplastin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcimycin/pharmacology
MH  - Calcium/metabolism
MH  - Calmodulin/*antagonists & inhibitors
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*drug effects/metabolism
MH  - Endotoxins/pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Infant, Newborn
MH  - Interleukin-1/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Sulfonamides/*pharmacology
MH  - Thromboplastin/*biosynthesis
MH  - Umbilical Veins
EDAT- 1994/02/15 00:00
MHDA- 1994/02/15 00:01
CRDT- 1994/02/15 00:00
PHST- 1994/02/15 00:00 [pubmed]
PHST- 1994/02/15 00:01 [medline]
PHST- 1994/02/15 00:00 [entrez]
AID - 10.1016/0049-3848(94)90096-5 [doi]
PST - ppublish
SO  - Thromb Res. 1994 Feb 15;73(3-4):177-84. doi: 10.1016/0049-3848(94)90096-5.