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Subject: LUPUS/OXIDATION/FREE RADICAL
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Biochem. Soc. Symp. 61: 1-31 (1995)[96232721]
Oxidative stress: the paradox of aerobic life.
K. J. Davies
Department of Biochemistry & Molecular Biology, Albany Medical
College, NY 12208, USA.
The paradox of aerobic life, or the 'Oxygen Paradox', is that higher
eukaryotic aerobic organisms cannot exist without oxygen, yet oxygen
is inherently dangerous to their existence. This 'dark side' of oxygen
relates directly to the fact that each oxygen atom has one unpaired
electron in its outer valence shell, and molecular oxygen has two
unpaired electrons. Thus atomic oxygen is a free radical and molecular
oxygen is a (free) bi-radical. Concerted tetravalent reduction of
oxygen by the mitochondrial electron-transport chain, to produce
water, is considered to be a relatively safe process; however, the
univalent reduction of oxygen generates reactive intermediates. The
reductive environment of the cellular milieu provides ample
opportunities for oxygen to undergo unscheduled univalent reduction.
Thus the superoxide anion radical, hydrogen peroxide and the extremely
reactive hydroxyl radical are common products of life in an aerobic
environment, and these agents appear to be responsible for oxygen
toxicity. To survive in such an unfriendly oxygen environment, living
organisms generate--or garner from their surroundings--a variety of
water- and lipid-soluble antioxidant compounds. Additionally, a series
of antioxidant enzymes, whose role is to intercept and inactivate
reactive oxygen intermediates, is synthesized by all known aerobic
organisms. Although extremely important, the antioxidant enzymes and
compounds are not completely effective in preventing oxidative damage.
To deal with the damage that does still occur, a series of damage
removal/repair enzymes, for proteins, lipids and DNA, is synthesized.
Finally, since oxidative stress levels may vary from time to time,
organisms are able to adapt to such fluctuating stresses by inducing
the synthesis of antioxidant enzymes and damage removal/repair
enzymes. In a perfect world the story would end here; unfortunately,
biology is seldom so precise. The reality appears to be that, despite
the valiant antioxidant and repair mechanisms described above,
oxidative damage remains an inescapable outcome of aerobic existence.
In recent years oxidative stress has been implicated in a wide variety
of degenerative processes, diseases and syndromes, including the
following: mutagenesis, cell transformation and cancer;
atherosclerosis, arteriosclerosis, heart attacks, strokes and
ischaemia/reperfusion injury; chronic inflammatory diseases, such as
rheumatoid arthritis, lupus erythematosus and psoriatic arthritis;
acute inflammatory problems, such as wound healing; photo-oxidative
stresses to the eye, such as cataract; central-nervous-system
disorders, such as certain forms of familial amyotrophic lateral
sclerosis, certain glutathione peroxidase-linked adolescent seizures,
Parkinson's disease and Alzheimer's dementia; and a wide variety of
age-related disorders, perhaps even including factors underlying the
aging process itself. Some of these oxidation-linked diseases or
disorders can be exacerbated, perhaps even initiated, by numerous
environmental pro-oxidants and/or pro-oxidant drugs and foods.
Alternatively, compounds found in certain foods may be able to
significantly bolster biological resistance against oxidants.
Currently, great interest centres on the possible protective value of
a wide variety of plant-derived antioxidant compounds, particularly
those from fruits and vegetables.
MeSH Terms:
* Antioxidants/metabolism
* DNA Damage
* Human
* Oxidative Stress*
* Oxygen/metabolism
* Radioactive Pollutants
* Reactive Oxygen Species
* Superoxide Dismutase/metabolism
Substances:
* Oxygen
* Reactive Oxygen Species
* Radioactive Pollutants
* Antioxidants
* Superoxide Dismutase
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From
Subject: LUPUS/OXIDATION/FREE RADICAL/COLLAGEN
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Z Rheumatol 39: 84-90 (1980)[81035511]
Chromosomal instability in collagen disease.
I. Emerit
Chromosome instability is observed in patients with collagen disease.
It is due to the presence of a chromosome-breaking agent in the serum
which also induces chromosome breaks and rearrangements in blood
cultures from healthy subjects. It is not possible to say at present
whether this breakage factor is identical to that in patients with
progressive systemic sclerosis, lupus erythematosus or rheumatoid
arthritis. In all three diseases the agent is a substance with a low
molecular weight between 1000 and 10,000 daltons. Since the enzyme
superoxide dismutase has an anticlastogenic protective effect, the
action of the agent on chromosomes is probably an indirect one, namely
by generation of oxygen-dependent free radicals such as O2- x and OH.
MeSH Terms:
* Animal
* Arthritis, Rheumatoid/physiopathology
* Cells, Cultured
* Chromosome Aberrations*
* Collagen Diseases/physiopathology
* Human
* Lupus Erythematosus, Systemic/physiopathology
* Mice
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