PMID- 15843586
OWN - NLM
STAT- MEDLINE
DCOM- 20050621
LR  - 20211203
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 174
IP  - 9
DP  - 2005 May 1
TI  - Inhibition of mammalian target of rapamycin potentiates thrombin-induced 
      intercellular adhesion molecule-1 expression by accelerating and stabilizing 
      NF-kappa B activation in endothelial cells.
PG  - 5823-9
AB  - We addressed the regulatory function of mammalian target of rapamycin (mTOR) in 
      the mechanism of thrombin-induced ICAM-1 gene expression in endothelial cells. 
      Pretreatment of HUVECs with rapamycin, an inhibitor of mTOR, augmented 
      thrombin-induced ICAM-1 expression. Inhibition of mTOR by this approach promoted 
      whereas over-expression of mTOR inhibited thrombin-induced transcriptional 
      activity of NF-kappaB, an essential regulator of ICAM-1 transcription. Analysis 
      of the NF-kappaB signaling pathway revealed that inhibition of mTOR potentiated 
      IkappaB kinase activation resulting in a rapid and persistent phosphorylation of 
      IkappaBalpha on Ser32 and Ser36, a requirement for IkappaBalpha degradation. 
      Consistent with these data, we observed a more efficient and stable nuclear 
      localization of RelA/p65 and, subsequently, the DNA binding activity of NF-kappaB 
      by thrombin following mTOR inhibition. These data define a novel role of mTOR in 
      down-regulating thrombin-induced ICAM-1 expression in endothelial cells by 
      controlling a delayed and transient activation of NF-kappaB.
FAU - Minhajuddin, Mohd
AU  - Minhajuddin M
AD  - Department of Pediatrics, University of Rochester School of Medicine, Rochester, 
      New York 14642, USA.
FAU - Fazal, Fabeha
AU  - Fazal F
FAU - Bijli, Kaiser M
AU  - Bijli KM
FAU - Amin, Md Ruhul
AU  - Amin MR
FAU - Rahman, Arshad
AU  - Rahman A
LA  - eng
GR  - HL67424/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
RN  - EC 3.4.21.5 (Thrombin)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - DNA-Binding Proteins/metabolism/physiology
MH  - Down-Regulation/drug effects
MH  - Drug Synergism
MH  - Endothelium, Vascular/cytology/drug effects/*enzymology/metabolism
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - I-kappa B Kinase
MH  - I-kappa B Proteins/metabolism
MH  - Intercellular Adhesion Molecule-1/*biosynthesis/metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*metabolism/physiology
MH  - Phosphorylation
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Protein Kinases/*metabolism/physiology
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Thrombin/antagonists & inhibitors/*pharmacology
EDAT- 2005/04/22 09:00
MHDA- 2005/06/23 09:00
CRDT- 2005/04/22 09:00
PHST- 2005/04/22 09:00 [pubmed]
PHST- 2005/06/23 09:00 [medline]
PHST- 2005/04/22 09:00 [entrez]
AID - 174/9/5823 [pii]
AID - 10.4049/jimmunol.174.9.5823 [doi]
PST - ppublish
SO  - J Immunol. 2005 May 1;174(9):5823-9. doi: 10.4049/jimmunol.174.9.5823.