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Lipid peroxidation
increases in a variety of tissues with advancing
age (Yu, 1993). Lipid peroxidation is a well-established
mechanism of cellular injury, leading to the destruction
of membrane lipids and the production of lipid peroxides
and their by-products, such as aldehydes. Malonaldehyde
(MDA) and 4-hydroxyalkenals, such as 4-HNE, are
end products derived from the breakdown of polyunsaturated
fatty acids and related esters. Measurement of such
aldehydes provides a convenient index of lipid peroxidation
(Esterbauer and Cheeseman, 1990).
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2005
Departments of Dermatology,
Faculty of Medicine, Zonguldak Karaelmas
University, Zonguldak, Turkey.
Background: The pathophysiology
of alopecia areata (AA) has not been clearly
defined; however, it appears as a tissue-restricted
autoimmune disease mediated by T lymphocytes.
Immunohistochemical studies have shown peri-
and infra-follicular inflammatory infiltrate
which damages hair follicles. We analyzed
the role of lipid peroxidation and oxidant-antioxidant
enzymes in the pathogenesis of AA. Material/Methods:
Twenty-four patients with AA and 20 age-
and sex-matched healthy controls were enrolled
in this study. We analyzed serum levels
of malondialdehyde (MDA) and nitric oxide
(NO) and the serum activities of superoxide
dismutase (SOD) and xanthine oxidase (XO)
in patients with AA and control subjects.
Results: The levels of MDA and NO (nitrite/nitrate)
and the activity of XO in serum of patients
with AA (0.76+/-0.34 nmol/ml, 14.88+/-6.40
nmol/ml, and 0.34+/-0.10 U/ml, respectively)
were significantly higher than those of
controls (0.35+/-0.09 nmol/ml, 10.71+/-1.75
nmol/ml, 0.11+/-0.03 U/ml; p<0.001, p<0.001,
p<0.05, respectively). The SOD activity
(12.95+/-2.16 U/ml) in the serum of patients
with AA was significantly lower than that
of controls (14.89+/-2.29 U/ml, p<0.05).
Conclusions: Increased lipid peroxidation
in AA may be related to an increase in NO
level and XO activity and a decrease in
SOD activity. These results suggest that
lipid peroxidation and alterations in the
oxidant-antioxidant enzymatic system may
play a role in the pathogenesis of AA.
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Division of Drug Target
Discovery and Development, Central Drug Research
Institute, Chatter Manzil Palace, Mahatma
Gandhi Marg, Lucknow 226001, Uttar Pradesh,
India.
Severe hemolysis or myolysis
occurring during pathological states, such
as sickle cell disease, ischemia reperfusion,
and malaria results in high levels of free
heme, causing undesirable toxicity leading
to organ, tissue, and cellular injury. Free
heme catalyzes the oxidation, covalent cross-linking
and aggregate formation of protein and its
degradation to small peptides. It also catalyzes
the formation of cytotoxic lipid peroxide
via lipid peroxidation and damages DNA through
oxidative stress. Heme being a lipophilic
molecule intercalates in the membrane and
impairs lipid bilayers and organelles, such
as mitochondria and nuclei, and destabilizes
the cytoskeleton. Heme is a potent hemolytic
agent and alters the conformation of cytoskeletal
protein in red cells. Free heme causes endothelial
cell injury, leading to vascular inflammatory
disorders and stimulates the expression
of intracellular adhesion molecules. Heme
acts as a pro-inflammatory molecule and
heme-induced inflammation is involved in
the pathology of diverse conditions; such
as renal failure, arteriosclerosis, and
complications after artificial blood transfusion,
peritoneal endometriosis, and heart transplant
failure. Heme offers severe toxic effects
to kidney, liver, central nervous system
and cardiac tissue. Although heme oxygenase
is primarily responsible to detoxify free
heme but other extra heme oxygenase systems
also play a significant role to detoxify
heme. A brief account of free heme toxicity
and its detoxification systems along with
mechanistic details are presented.
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2002
Departments of Genetics
and Medical Genetics, University of Wisconsin,
445 Henry Mall, Madison, WI 53706, USA.
To examine molecular events
associated with brain aging and its retardation
by caloric restriction (CR), we have employed
high-density oligonucleotide arrays providing
data on 6347 genes to define transcriptional
patterns in two brain regions (cerebellum
and neocortex). Male C57BL/6 mice were either
fed normally or subjected to CR. To investigate
aging, 5 month (young adult) and 30 month-old
normally fed mice were compared. To study
CR, 30 month-old control and CR mice were
compared. In both brain regions, aging resulted
in a gene expression profile suggestive
of a marked inflammatory response, oxidative
stress and reduced neuronal plasticity and
neurotrophic support. In the brain, CR selectively
attenuated the age-associated induction
of genes encoding inflammatory and stress
responses. In addition to providing an improved
understanding of the aging process, the
use of DNA microarrays generates panels
of hundreds of transcriptional biomarkers
of molecular aging, providing a new tool
to measure biological age on a tissue-specific
basis. These studies suggest that genomic
approaches may be useful in understanding
the molecular basis of the aging process
in experimental animals.
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2000
Gerontology
Research Center, NIA/NIH, Baltimore, MD
21224, USA.
Aging is accompanied by
a decline of functions controlled by the
central dopaminergic system, such as reduced
locomotor activity, motivation, impairment
of memory formation, and learning deficits.
The molecular mechanisms underlying age-related
impairment of dopaminergic functions are
unknown. Current literature and our own
recent work, which are reviewed and summarized
in the present paper, suggest that dopamine
oxidative stress and its subsequent signaling
may contribute to the aging of dopaminergic
system.
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