Role of advanced glycation end products in cellular signaling

Redox Biol. 2014 Jan 9;2:411-29. doi: 10.1016/j.redox.2013.12.016. eCollection 2014.

Abstract

Improvements in health care and lifestyle have led to an elevated lifespan and increased focus on age-associated diseases, such as neurodegeneration, cardiovascular disease, frailty and arteriosclerosis. In all these chronic diseases protein, lipid or nucleic acid modifications are involved, including cross-linked and non-degradable aggregates, such as advanced glycation end products (AGEs). Formation of endogenous or uptake of dietary AGEs can lead to further protein modifications and activation of several inflammatory signaling pathways. This review will give an overview of the most prominent AGE-mediated signaling cascades, AGE receptor interactions, prevention of AGE formation and the impact of AGEs during pathophysiological processes.

Keywords: ADAMST, a disintegrin and metalloproteinase with a thrombospondin type 1 motif; AGE, advanced glycation end products; AGE-receptors; Advanced glycation end products; Age-associated diseases; Aggregates; Aging; E, from embryonic day; EGFR, epidermal growth factor receptor; ERK, extracellular-signal regulated kinase; F3NK, fructosamine 3-phosphokinase; FKHRL1, forkhead transcription factor; HDL, high density lipoprotein; HMGB1, high-mobility-group-protein B1; HNE, 4-hydroxy-trans-2-nonenal; Jak1/2, Janus kinase 1/2; LDL, low density lipoprotein; MDA, malondialdehyde; MEKK, mitogen-activated protein/ERK kinase kinases; MnSOD, manganese superoxide dismutase; NF-κB; Nf-κB, nuclear factor-light-chain-enhancer of activated B; Oxidative stress; PIK3, phosphoinositol 3 kinase; RAGE; RAGE, receptor of AGEs; RCC, reactive carbonyl compounds; Reactive carbonyl compounds; S100B, S100 calcium binding protein B; SIRt1, NAD+-dependent deacetylase and survival factor 1; SR-A, scavenger receptor class A; Signaling; Stat 1/2, signal transducers and activators of transcription 1/2; VSMC, vascular smooth muscle cells.

Publication types

  • Review

MeSH terms

  • Aging / physiology
  • Animals
  • Bone and Bones / metabolism
  • Dietary Proteins / adverse effects
  • Dietary Proteins / pharmacokinetics
  • Glycation End Products, Advanced / physiology*
  • Humans
  • Hyperglycemia / metabolism
  • Immune System / metabolism
  • Inflammation / etiology*
  • Inflammation / metabolism
  • Lipid Peroxidation
  • Lung / metabolism
  • Maillard Reaction
  • Models, Biological
  • NF-kappa B / physiology
  • Neurons / metabolism
  • Oxidative Stress / physiology
  • Polymers / metabolism
  • Protein Aggregates
  • Protein Transport
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / physiology*
  • Receptors, Scavenger / physiology
  • Signal Transduction / physiology*

Substances

  • Dietary Proteins
  • Glycation End Products, Advanced
  • NF-kappa B
  • Polymers
  • Protein Aggregates
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Receptors, Scavenger
  • polyol