Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress

Harry M. Lander, James M. Tauras, Jason S. Ogiste, Osamu Hori, Rebecca A. Moss, Ann Marie Schmidt

Research output: Contribution to journalArticle

625 Citations (Scopus)

Abstract

Advanced glycation end products (AGEs) exert their cellular effects on cells by interacting with specific cellular receptors, the best characterized of which is the receptor for AGE (RAGE). The transductional processes by which RAGE ligation transmits signals to the nuclei of cells is unknown and was investigated. AGE-albumin, a prototypic ligand, activated p21(ras) in rat pulmonary artery smooth muscle cells that express RAGE, whereas nonglycated albumin was without effect. MAP kinase activity was enhanced at concentrations of AGE-albumin, which activated p21(ras) and NF-κB. Depletion of intracellular glutathione rendered cells more sensitive to AGE-mediated activation of this signaling pathway. In contrast, signaling was blocked by preventing p21(ras) from associating with the plasma membrane or mutating Cys118 on p21(ras) to Ser. Signaling was receptor-dependent, because it was prevented by blocking access to RAGE with either anti-RAGE IgG or by excess soluble RAGE. These data suggest that RAGE-mediated induction of cellular oxidant stress triggers a cascade of intracellular signals involving p21(ras) and MAP kinase, culminating in transcription factor activation. The molecular mechanism that triggers this pathway likely involves oxidant modification and activation of p21(ras).

Original languageEnglish (US)
Pages (from-to)17810-17814
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number28
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins p21(ras)
Mitogen-Activated Protein Kinases
Oxidants
Chemical activation
Albumins
Phosphotransferases
IgG Receptors
Advanced Glycosylation End Products
Cell membranes
Advanced Glycosylation End Product-Specific Receptor
Cell Nucleus
Transcriptional Activation
Pulmonary Artery
Smooth Muscle Myocytes
Glutathione
Ligation
Muscle
Rats
Transcription Factors
Immunoglobulin G

ASJC Scopus subject areas

  • Biochemistry

Cite this

Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress. / Lander, Harry M.; Tauras, James M.; Ogiste, Jason S.; Hori, Osamu; Moss, Rebecca A.; Schmidt, Ann Marie.

In: Journal of Biological Chemistry, Vol. 272, No. 28, 1997, p. 17810-17814.

Research output: Contribution to journalArticle

Lander, Harry M. ; Tauras, James M. ; Ogiste, Jason S. ; Hori, Osamu ; Moss, Rebecca A. ; Schmidt, Ann Marie. / Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 28. pp. 17810-17814.
@article{d8a1a77497ec4b3b94920c23bc8484b2,
title = "Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress",
abstract = "Advanced glycation end products (AGEs) exert their cellular effects on cells by interacting with specific cellular receptors, the best characterized of which is the receptor for AGE (RAGE). The transductional processes by which RAGE ligation transmits signals to the nuclei of cells is unknown and was investigated. AGE-albumin, a prototypic ligand, activated p21(ras) in rat pulmonary artery smooth muscle cells that express RAGE, whereas nonglycated albumin was without effect. MAP kinase activity was enhanced at concentrations of AGE-albumin, which activated p21(ras) and NF-κB. Depletion of intracellular glutathione rendered cells more sensitive to AGE-mediated activation of this signaling pathway. In contrast, signaling was blocked by preventing p21(ras) from associating with the plasma membrane or mutating Cys118 on p21(ras) to Ser. Signaling was receptor-dependent, because it was prevented by blocking access to RAGE with either anti-RAGE IgG or by excess soluble RAGE. These data suggest that RAGE-mediated induction of cellular oxidant stress triggers a cascade of intracellular signals involving p21(ras) and MAP kinase, culminating in transcription factor activation. The molecular mechanism that triggers this pathway likely involves oxidant modification and activation of p21(ras).",
author = "Lander, {Harry M.} and Tauras, {James M.} and Ogiste, {Jason S.} and Osamu Hori and Moss, {Rebecca A.} and Schmidt, {Ann Marie}",
year = "1997",
doi = "10.1074/jbc.272.28.17810",
language = "English (US)",
volume = "272",
pages = "17810--17814",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "28",

}

TY - JOUR

T1 - Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress

AU - Lander, Harry M.

AU - Tauras, James M.

AU - Ogiste, Jason S.

AU - Hori, Osamu

AU - Moss, Rebecca A.

AU - Schmidt, Ann Marie

PY - 1997

Y1 - 1997

N2 - Advanced glycation end products (AGEs) exert their cellular effects on cells by interacting with specific cellular receptors, the best characterized of which is the receptor for AGE (RAGE). The transductional processes by which RAGE ligation transmits signals to the nuclei of cells is unknown and was investigated. AGE-albumin, a prototypic ligand, activated p21(ras) in rat pulmonary artery smooth muscle cells that express RAGE, whereas nonglycated albumin was without effect. MAP kinase activity was enhanced at concentrations of AGE-albumin, which activated p21(ras) and NF-κB. Depletion of intracellular glutathione rendered cells more sensitive to AGE-mediated activation of this signaling pathway. In contrast, signaling was blocked by preventing p21(ras) from associating with the plasma membrane or mutating Cys118 on p21(ras) to Ser. Signaling was receptor-dependent, because it was prevented by blocking access to RAGE with either anti-RAGE IgG or by excess soluble RAGE. These data suggest that RAGE-mediated induction of cellular oxidant stress triggers a cascade of intracellular signals involving p21(ras) and MAP kinase, culminating in transcription factor activation. The molecular mechanism that triggers this pathway likely involves oxidant modification and activation of p21(ras).

AB - Advanced glycation end products (AGEs) exert their cellular effects on cells by interacting with specific cellular receptors, the best characterized of which is the receptor for AGE (RAGE). The transductional processes by which RAGE ligation transmits signals to the nuclei of cells is unknown and was investigated. AGE-albumin, a prototypic ligand, activated p21(ras) in rat pulmonary artery smooth muscle cells that express RAGE, whereas nonglycated albumin was without effect. MAP kinase activity was enhanced at concentrations of AGE-albumin, which activated p21(ras) and NF-κB. Depletion of intracellular glutathione rendered cells more sensitive to AGE-mediated activation of this signaling pathway. In contrast, signaling was blocked by preventing p21(ras) from associating with the plasma membrane or mutating Cys118 on p21(ras) to Ser. Signaling was receptor-dependent, because it was prevented by blocking access to RAGE with either anti-RAGE IgG or by excess soluble RAGE. These data suggest that RAGE-mediated induction of cellular oxidant stress triggers a cascade of intracellular signals involving p21(ras) and MAP kinase, culminating in transcription factor activation. The molecular mechanism that triggers this pathway likely involves oxidant modification and activation of p21(ras).

UR - http://www.scopus.com/inward/record.url?scp=0030859290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030859290&partnerID=8YFLogxK

U2 - 10.1074/jbc.272.28.17810

DO - 10.1074/jbc.272.28.17810

M3 - Article

VL - 272

SP - 17810

EP - 17814

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 28

ER -