Chemistry Reference
In-Depth Information
scientific organizations have demonstrated a significantly increased interest in the
concept, and new societies have even been founded with the main goal to investi-
gate the effects on health and well-being of AGEs/ALEs in foods. The New York
Academy of Science appears to have taken the lead and a large number of scientific
contributions about AGEs/ALEs are published each year in its annals. In excess of
5000 titles about AGE and ALE are registered on PubMed, in addition to another
14,000 titles about the glycated hemoglobin, HbA
1c
.
Several methods are available for measurement of content of AGEs/ALEs in
body fluids and tissues: immunohistochemistry with polyclonal or monoclonal anti-
bodies, high-performance liquid chromatography (HPLC), and mass spectrography.
A large proportion, but not all, of these substances are autofluorescing,12,13
12,13
even if
not visible to the human eye. Often studied substances such as CML and CEL have
no fluorescing ability or any color. Despite that, measuring fluorescence is an excel-
lent method especially for screening of individuals with suspected high levels of
AGEs/ALEs in the body, but also for screening of foods suspected to be rich in these
dysfunctioning proteins. The fluorescence has its maximum at wavelengths between
350 and 440 nm.
12
7.4 rAgE: A rECEPTor AND MAsTEr sWITCh—A
kEy ACTor IN INFlAMMATIoN
RAGE is a prominent member of what has been called the immunoglobulin
superfamily of cell surface molecules. It is described as a “master switch” with the
ability to coordinate the inflammatory reaction in the body. RAGE induces a long-
lasting activation of the proinflammatory transcription factor NF-κβ and suppresses
a series of endogenous autoregulatory functions.
14 -17
Increased deposition of AGEs/
ALEs in tissues is suggested as a key element in the development of metabolic syn-
drome.
18,19
AGE/ALE accumulation and subsequent activation of RAGE are reported
to induce a significant downregulation of leptin in adipose cells.
20
Pronounced effects
of RAGE activation are often observed on endothelial cells, where increased expres-
sion of a long row of molecules, such as VCAM-1, ICAM-1, E-selectin, eNOS, TGF-
β, TNF-α, IL-6, PAI-1, and VEGF, are induced.
21
Strong RAGE-induced effects are
often reported on immune cells, macrophages,
22
and dendritic cells,
23,24
as well as
on smooth muscle, particularly in the walls of blood vessels, under the mucosa and
in the skin,
25
and associated with subsequent reduction in regenerative capacity and
function of the cells, increased blood pressure, and with development of chronic
diseases or exacerbation of complications to chronic diseases.
26
AGEs/ALEs accumulated in endothelial cells can be significantly reduced by
control of intake of foods rich in these substances. The situation is different in tissues
with low regenerative capacity and long life length, such as myelin- and collagen-
rich structures, where the substances risk staying forever: brain, peripheral nerves,
skeleton muscles, tendons, joints, skin, and eye, especially the lens. More recent
research has demonstrated the existence of an endogenous soluble form of RAGE
called sRAGE, which acts as a decoy for RAGE and prevents accumulation of RAGE
