0071509674.pdf

cell surface molecules. In addition, to its role in diabetes, RAGE interacts
with molecular pathways that regulate homeostasis, development, and
inflammation and plays a role in pathological conditions such as
Alzheimer’s disease and diabetes mellitus. Binding of a ligand to RAGE acti-
vates key cell signaling pathways, such as p21 (ras), MAP kinases, and NF-
kappa-B (NFκB), thereby reprogramming cellular characteristics. The
interactions and terminology are further complicated by the presence of
ENRAGE (extracellular newly identified RAGE-binding protein) that inter-
acts with cellular RAGE on endothelial cells, macrophages, lymphocytes,
and other cells to activate proinflammatory mediators. Interactions
between AGE, RAGE, and ENRAGE may explain many diabetic complica-
tions including delayed wound healing. AGE derivatization is probably
nonspecific and involves not only basal lamina-specific molecules, but also
a vast array of extracellular and intracellular proteins (transcription factors,
structural proteins, and membrane transporters). Hence, cellular coordina-
tion/communication becomes slowly but progressively hampered in the
kidney and other organs.

Urinary System Answers 395

Dangers of Diabetic Hyperglycemia

GLUCOSE

amino acids

degradation or

metabolism

Reactive

intermediates

circulating proteins or

matrix proteins

in basement membrane,

connective tissue

Advanced Glycated

End-Products (AGE)

AGE receptor (RAGE)

Endothelial leakage,

thicker BM, generation

of immunogenicity

Decreased cell

potential, lower

conduction speeds,

generation of ROS

Apoptosis

hemiacetal aldehyde

AGE = advanced glycation end-products,

RAGE = age receptor,

BM = basement membrane,

ROS = reactive oxygen species