Biomedical Engineering Reference
In-Depth Information
underlying various chronic inl ammatory diseases. h e deleterious roles of
inl ammatory AMs underline age-related pathophysiological conditions.
In this chapter, we review the deleterious roles of AMs by focusing on (1)
altered AMs by age-related redox mediators, (2) alterations of AMs during aging,
(3) mechanisms underlining inl ammatory AM changes during aging, (4) the role
of AMs in age-related diseases, and (5) possible interventions in age-related AM
changes.
INTRODUCTION
Adhesion molecules (AMs) are a group of membrane proteins exposed on the cell
surface that adhere to other cells or to the extracellular matrix in a process known
as cell adhesion. AM proteins basically function as receptors and are composed of
three domains: an intracellular domain that interacts with the cytoskeleton, a trans-
membrane domain, and an extracellular domain that interacts with either other
AMs or with the extracellular matrix through homophilic or heterophilic binding.
When undergoing proteolytic cleavage, AMs release the soluble ectodomain from
the cell surface, resulting in circulating or a soluble form of AMs (sAMs). Most
AMs are classii ed into four protein families: immunoglobulin (Ig) superfamily,
integrins, cadherins and selectins.
One of the deleterious roles of AMs is their participation in the inl ammation
process. For instance, in response to pro-inl ammatory cytokines and chemokines
such as tumor necrosis factor-α (TNF-α) and interleukin 1-β (IL-1β), AMs direct
leukocyte-endothelial cell (EC) interactions through a sequential process of
tethering, rolling, adhesion and transmigration. When acting as macrophages,
leukocytes pass through the tight junction between ECs and ini ltrate into the
vessel wall, where they release various inl ammatory mediators, thereby triggering
further inl ammation. Consequently, prolonged, unchecked inl ammatory AMs
lead to chronic inl ammatory conditions. To distinguish among the AMs, the AMs
that participate in the inl ammatory process are called inl ammatory AMs in this
chapter.
Aging is a complex biological phenomenon that is characterized as a progressive,
physiological deterioration with time, accompanied by increased vulnerability
to pathogenesis. Although the underlying cause and mechanisms of aging are
unknown, the popular oxidative stress theory of aging provides molecular insights
into possible causative factors for the aging process (Yu and Chung 2006). According
to the tenets of this theory, the combined ef ects of accumulated oxidative damage
and weakened antioxidative defense systems cause a disturbance in the organism's
redox balance.
However, one of the most intriguing and important questions is, how does
a disrupted redox balance increase the vulnerability to disease during aging?
h e answer could be found in the age-associated activation of redox-sensitive
