Biomedical Engineering Reference
In-Depth Information
second electron reduction or enzymatically catalyzed by superoxide
dismutase, or the highly reactive hydroxyl radical via the Fenton
reaction with hydrogen peroxide. Hydroxyl radical can oxidatively
damage cellular macromolecules including proteins, DNA, and lipids
(Halliwell and Gutteridge, 2007).
Protein Oxidation Protein oxidation can impair the function of signal
transduction proteins, receptors, and enzymes and subsequently cause
secondary damage to other cellular macromolecules. If damage occurs
toDNArepair enzymes, levelsofDNAdamagecan increase,whiledamage
to DNA polymerases may decrease replication fidelity (Halliwell and
Gutteridge, 2007).Oxidizedproteinmayberecognizedasa foreignantigen
by the innate immune system and trigger antibody production (Peng et al.,
1997).Oxidationofa protein is initiatedby the hydroxyl radical-dependent
abstraction of the
a
-hydrogen atom of an amino acid residue to form a
carbon-centered radical, which can rapidly react with oxygen to form
subsequent radical intermediates that can react with other amino acid
residues in the same or a different protein, forming a new carbon-centered
radical (Berlett and Stadtman, 1997). All amino acid side chains are
susceptible to attack by hydroxyl radicals. A well-studied measure of
protein oxidation is protein carbonyl formation. Carbonyl groups can be
introduced into proteins either by direct metal-catalyzed oxidation of
lysine, arginine, proline, and threonine residues, or by reaction with
aldehydes produced during lipid peroxidation, such as 4-hydroxy-2-none-
nal (HNE), and malondialdehyde (MDA), or with reactive carbonyl
derivatives (Berlett and Stadtman, 1997; Nystrom, 2005). Histidine
attacked by the reactive lipid peroxidation aldehyde product HNE can
generate anHNE-histidine adduct that canbemeasuredas amarker of lipid
peroxidation (UchidaandStadtman, 1992) (Figure7.21). Oxidizedprotein
products are removed from the cell by increased recognition and degrada-
tionbycellularproteases,andlossofdevelopmentallyimportantproteins in
theembryocanleadtosubsequentembryopathies,whichhasbeenobserved
with phenytoin-initiated protein oxidation (Winn and Wells, 1999;
Nystrom, 2005). The presence of elevated levels of carbonylated proteins
has been used as amarker of ROS-mediated protein oxidation, and several
methods of detection have been developed (Levine et al., 1994).
