PMID- 10531386
OWN - NLM
STAT- MEDLINE
DCOM- 19991216
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 44
DP  - 1999 Oct 29
TI  - N(epsilon)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for
      advanced glycation end products that activate cell signaling pathways and
      modulate gene expression.
PG  - 31740-9
AB  - Recent studies suggested that interruption of the interaction of advanced
      glycation end products (AGEs), with the signal-transducing receptor receptor for 
      AGE (RAGE), by administration of the soluble, extracellular ligand-binding domain
      of RAGE, reversed vascular hyperpermeability and suppressed accelerated
      atherosclerosis in diabetic rodents. Since the precise molecular target of
      soluble RAGE in those settings was not elucidated, we tested the hypothesis that 
      predominant specific AGEs within the tissues in disorders such as diabetes and
      renal failure, N(epsilon)-(carboxymethyl)lysine (CML) adducts, are ligands of
      RAGE. We demonstrate here that physiologically relevant CML modifications of
      proteins engage cellular RAGE, thereby activating key cell signaling pathways
      such as NF-kappaB and modulating gene expression. Thus, CML-RAGE interaction
      triggers processes intimately linked to accelerated vascular and inflammatory
      complications that typify disorders in which inflammation is an established
      component.
FAU - Kislinger, T
AU  - Kislinger T
AD  - College of Physicians & Surgeons, Columbia University, New York, New York 10032, 
      USA.
FAU - Fu, C
AU  - Fu C
FAU - Huber, B
AU  - Huber B
FAU - Qu, W
AU  - Qu W
FAU - Taguchi, A
AU  - Taguchi A
FAU - Du Yan, S
AU  - Du Yan S
FAU - Hofmann, M
AU  - Hofmann M
FAU - Yan, S F
AU  - Yan SF
FAU - Pischetsrieder, M
AU  - Pischetsrieder M
FAU - Stern, D
AU  - Stern D
FAU - Schmidt, A M
AU  - Schmidt AM
LA  - eng
GR  - DK52495/DK/NIDDK NIH HHS/United States
GR  - HL56881/HL/NHLBI NIH HHS/United States
GR  - HL60901/HL/NHLBI NIH HHS/United States
GR  - etc.
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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Serum Albumin)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 70YDX3Z2O7 (N(6)-carboxymethyllysine)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus
MH  - Endothelium, Vascular/cytology/metabolism
MH  - Gene Expression Regulation
MH  - *Glycation End Products, Advanced
MH  - Humans
MH  - Lung/metabolism
MH  - Lysine/*analogs & derivatives/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Muscle, Smooth, Vascular/metabolism
MH  - NF-kappa B/metabolism
MH  - Phagocytes/metabolism
MH  - Protein Binding
MH  - Protein Processing, Post-Translational
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/*metabolism
MH  - Renal Insufficiency
MH  - Serum Albumin/*metabolism
MH  - Signal Transduction
MH  - Vascular Cell Adhesion Molecule-1/biosynthesis
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1074/jbc.274.44.31740 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 29;274(44):31740-9. doi: 10.1074/jbc.274.44.31740.