PMID- 14720501
OWN - NLM
STAT- MEDLINE
DCOM- 20040227
LR  - 20211203
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 292
IP  - 1
DP  - 2004 Jan 1
TI  - Ebselen inhibits tumor necrosis factor-alpha-induced c-Jun N-terminal kinase 
      activation and adhesion molecule expression in endothelial cells.
PG  - 1-10
AB  - Tumor necrosis factor-alpha (TNF-alpha) stimulates expression of endothelial cell 
      (EC) genes that may promote atherosclerosis in part by an activation of 
      mitogen-activated protein (MAP) kinases. Ebselen 
      (2-phenyl-1,2-benzisoselenazol-3[2H]-one), a selenoorganic compound, is effective 
      for acute ischemic stroke; however, its effect on EC has not yet been elucidated. 
      We examined the effect of ebselen on TNF-alpha-induced MAP kinase activation and 
      adhesion molecule expression in cultured human umbilical vein endothelial cells 
      (HUVEC). Extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase 
      (JNK) and p38 were rapidly and significantly activated by TNF-alpha in HUVEC. 
      TNF-alpha-induced JNK activation was inhibited by ebselen, whereas ERK1/2 and p38 
      were not affected. Apoptosis signal-regulated kinase 1 (ASK1) was suggested to be 
      involved in TNF-alpha-induced JNK activation because transfection of 
      kinase-inactive ASK1 inhibited TNF-alpha-induced JNK activation. Ebselen 
      inhibited TNF-alpha-induced TNF receptor-associated factor 2 (TRAF2)-ASK1 complex 
      formation and phosphorylation of stress-activated protein kinase ERK kinase 1 
      (SEK1), which is an upstream signaling molecule of JNK. Finally, 
      TNF-alpha-induced activator protein-1 (AP-1) and nuclear factor-kappaB 
      (NF-kappaB) activation and resultant intracellular adhesion molecule-1 (ICAM-1) 
      and vascular cell adhesion molecule-1 (VCAM-1) expressions were inhibited by 
      ebselen. Specific inhibitors for JNK and NF-kappaB also inhibited 
      TNF-alpha-induced ICAM-1 and VCAM-1 expressions in HUVEC. These findings suggest 
      that ebselen prevents TNF-alpha-induced EC activation through the inhibition of 
      TRAF2-ASK1-SEK1 signaling pathway, which leads to JNK activation. Inhibition of 
      JNK by ebselen may imply its usefulness for the prevention of atherosclerosis 
      relevant to EC activation.
FAU - Yoshizumi, Masanori
AU  - Yoshizumi M
AD  - Department of Pharmacology, The University of Tokushima School of Medicine, 
      Tokushima 770-8503, Japan. yoshizu@basic.med.tokushima-u.ac.jp
FAU - Fujita, Yoshiko
AU  - Fujita Y
FAU - Izawa, Yuki
AU  - Izawa Y
FAU - Suzaki, Yuki
AU  - Suzaki Y
FAU - Kyaw, Moe
AU  - Kyaw M
FAU - Ali, Nermin
AU  - Ali N
FAU - Tsuchiya, Koichiro
AU  - Tsuchiya K
FAU - Kagami, Shoji
AU  - Kagami S
FAU - Yano, Seiji
AU  - Yano S
FAU - Sone, Saburo
AU  - Sone S
FAU - Tamaki, Toshiaki
AU  - Tamaki T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Azoles)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Isoindoles)
RN  - 0 (NF-kappa B)
RN  - 0 (Organoselenium Compounds)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 40X2P7DPGH (ebselen)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 2.7.12.2 (MAP2K4 protein, human)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Azoles/*pharmacology
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*drug effects/metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Isoindoles
MH  - JNK Mitogen-Activated Protein Kinases
MH  - *MAP Kinase Kinase 4
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Mitogen-Activated Protein Kinases/*biosynthesis
MH  - NF-kappa B/metabolism
MH  - Organoselenium Compounds/*pharmacology
MH  - Phosphorylation
MH  - Time Factors
MH  - Transcription Factor AP-1/metabolism
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/metabolism
MH  - Umbilical Veins/cytology
MH  - Vascular Cell Adhesion Molecule-1/metabolism
EDAT- 2004/01/15 05:00
MHDA- 2004/02/28 05:00
CRDT- 2004/01/15 05:00
PHST- 2004/01/15 05:00 [pubmed]
PHST- 2004/02/28 05:00 [medline]
PHST- 2004/01/15 05:00 [entrez]
AID - S0014482703004439 [pii]
AID - 10.1016/j.yexcr.2003.08.003 [doi]
PST - ppublish
SO  - Exp Cell Res. 2004 Jan 1;292(1):1-10. doi: 10.1016/j.yexcr.2003.08.003.