Biomedical Engineering Reference
In-Depth Information
Figure 8
Cellular and molecular responses of 4-hydroxy-2-nonenal.
peroxidation, is known to induce
=
regulate various cellular events, such as
proliferation, apoptosis, and activation of MAP kinase signaling pathways
(17,18) (Fig. 8). 4-HNE has a high affinity towards cysteine, histidine, and
lysine residues. It forms adducts with proteins, altering their function. It also
acts as a chemoattractant for neutrophils in vitro and in vivo (18). Recent
data indicate increased 4-HNE-modified protein levels in airway and alveolar
epithelial cells, endothelial cells, and neutrophils in subjects with airway
obstruction, compared to subjects without airway obstruction (19) (Fig. 9a
and b). Levels of 4-HNE-adducts in alveolar and airway epithelium have
been shown to be inversely related to the FEV
1
, suggesting a role for 4-
HNE in the pathogenesis of COPD. Products of lipid peroxidation have been
found in increased amounts in the lungs of cigarette smokers, and the levels
relate to the length of the smoking history. Increased levels of 4-HNE adducts
in lungs of COPD patients are further confirmed by Aoshiba et al.(20) who
have recently showed that cigarette smoking enhanced the levels of 4-HNE
adducts in bronchiolar epithelial and alveolar type cells in mice. Thus
evidence is accumulating that cigarette smoke triggers oxidative stress leading
to lipid peroxidation in lungs of smokers and patients with COPD.
VII.
SYSTEMIC OXIDATIVE STRESS
COPD is now considered to have not only local lung, but systemic manifes-
tations. One manifestation of a systemic effect is the presence of markers of
