Anat Cell Biol.  2012 Mar;45(1):47-52. 10.5115/acb.2012.45.1.47.

Activated microglial cells synthesize and secrete AGE-albumin

• Byun K
• Bayarsaikhan E
• Kim D
• Son M
• Hong J
• Jeong GB
• Paek SH
• Won MH
• Lee B

• KMID: 1447452
• DOI: http://doi.org/10.5115/acb.2012.45.1.47

Abstract

A holy grail of curing neurodegenerative diseases is to identify the main causes and mechanisms underlying neuronal death. Many studies have sought to identify these targets in a wide variety of ways, but a more important task is to identify critical molecular targets and their origins. Potential molecular targets include advanced glycation end products (AGEs) that can promote neuronal cell death, thereby contributing to neurodegenerative disorders such as Alzheimer disease or Parkinson disease. In this study, we showed that AGE-albumin (glycated albumin) is synthesized in microglial cells and secreted in the human brain. Our results provide new insight into which microglial cells can promote the receptor for AGE-mediated neuronal cell death, eventually leading to neurodegenerative diseases.

Keyword

Microglia; AGE albumin; Cell death

MeSH Terms

Alzheimer Disease
Brain
Cell Death
Glycosylation End Products, Advanced
Humans
Microglia
Neurodegenerative Diseases
Neurons
Parkinson Disease
Glycosylation End Products, Advanced

Figure

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  Fig. 1 Distribution and synthesis of advanced glycation end products (AGE)-albumin in human microglial cells and rat brain. Triple-labeled confocal microscopy was used to study the distribution and relative levels of albumin (ALB, green), AGE (red) and a specific marker of microglial cells (Iba1, blue) in the human microglial cell line, human primary microglial cells, and entorhinal cortex of rat brain after amyloid β (Aβ) treatment. Scale bar=50 µm.

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  Fig. 2 Relationship between advanced glycation end products (AGE)-albumin (ALB) and amyloid β (Aβ) contributing to Aβ aggregation. (A) Co-localization of albumin (blue), AGE (red), and ThT fluorescence (green) in amyloid plaques in Aβ-treated rat brains and human Alzheimer disease (AD) brains were evaluated by triple-labeled fluorescent microscopic images. (B) In teraction between AGE-ALB and Aβ, contributing to increased synthesis and aggregation of Aβ. Proximity ligation O-Link analysis was performed by fluorescent microscopic images to determine the relative extents of interaction (red spots) between ALB and Aβ in human microglial cells and rat brains before and after Aβ treatment, as well as human brains from normal and AD individuals, respectively. The average numbers of blob per cell from each sample are compared in bar graphs. Scale bars=50 µm.

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  Fig. 3 Relative changes in advanced glycation end products (AGE) and receptor protein for AGEs (RAGE) interactions. (A) Proximity ligation assay was performed using fluorescent microscopy images to determine the relative extents of interaction (red spots) between AGE and RAGE in the rat brains before or after amyloid β (Aβ) treatment. Scale bar=50 µm. (B) The average number of blobs per cell from each sample is summarized in bar graphs.

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  Fig. 4 Induction of the neuronal mitogen-activated protein kinases (MAPK) pathway by advanced glycation end products (AGE)-albumin (ALB). Double confocal microscopy images simultaneously show relative levels of extracellular signal-regulated kinases 1 and 2 (ERK1/2), pERK1/2, p38K, pp38K, stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK), pSAPK/JNK (green), or DAPI (blue) in human primary neuronal cells before and after AGE-ALB treatment for 6 h. Scale bar=50 µm.

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