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Sat, Apr-30-05, 17:18
J Biol Chem. 2005 Apr 25; [Epub ahead of print] Related
Articles, Links
Reactive carbonyls and polyunsaturated fatty acids produce a
hydroxyl radical-like species: A potential pathway for
oxidative damage of retinal proteins in diabetes.
Pennathur S, Ido Y, Heller JI, Byun J, Danda R, Pergola P,
Williamson JR, Heinecke JW.
Department of Medicine, Division of Endocrinology, Diabetes
and Metabolism, University of Washington, Seattle, WA 98195.
The pattern of oxidized amino acids in aortic proteins of
nonhuman primates suggests that a species resembling hydroxyl
radical damages proteins when blood glucose levels are high.
However, recent studies argue strongly against a generalized
increase in diabetic oxidative stress, which might instead be
confined to the vascular wall. Here, we describe a pathway for
glucose-stimulated protein oxidation and provide evidence of
its complicity in diabetic microvascular disease. Low density
lipoprotein incubated with pathophysiological concentrations
of glucose became selectively enriched in ortho-tyrosine and
meta-tyrosine, implicating a hydroxyl radical-like species in
protein damage. Model system studies demonstrated that the
reaction pathway requires both a reactive carbonyl group and a
polyunsaturated fatty acid, involves lipid peroxidation, and
is blocked by the carbonyl scavenger aminoguanidine. To
explore the physiological relevance of the pathway, we used
mass spectrometry and HPLC to quantify oxidation products in
control and hyperglycemic rats. Hyperglycemia raised levels of
ortho-tyrosine, meta-tyrosine, and oxygenated lipids in the
retina, a tissue rich in polyunsaturated fatty acids. Rats
that received aminoguanidine also did not show this increase
in protein and lipid oxidation. In contrast, hyperlipidemia in
the absence of hyperglycemia failed to increase protein and
lipid oxidation products in the retina. Our observations
suggest that generation of a hydroxyl radical-like species by
a carbonyl/polyunsaturated fatty acid pathway might promote
localized oxidative stress in tissues vulnerable to diabetic
damage. This raises the possibility that antioxidant therapies
that specifically inhibit the pathway might delay the vascular
complications of diabetes.
PMID: 15855169 [PubMed - as supplied by publisher]
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Articles, Links
Reactive carbonyls and polyunsaturated fatty acids produce a
hydroxyl radical-like species: A potential pathway for
oxidative damage of retinal proteins in diabetes.
Pennathur S, Ido Y, Heller JI, Byun J, Danda R, Pergola P,
Williamson JR, Heinecke JW.
Department of Medicine, Division of Endocrinology, Diabetes
and Metabolism, University of Washington, Seattle, WA 98195.
The pattern of oxidized amino acids in aortic proteins of
nonhuman primates suggests that a species resembling hydroxyl
radical damages proteins when blood glucose levels are high.
However, recent studies argue strongly against a generalized
increase in diabetic oxidative stress, which might instead be
confined to the vascular wall. Here, we describe a pathway for
glucose-stimulated protein oxidation and provide evidence of
its complicity in diabetic microvascular disease. Low density
lipoprotein incubated with pathophysiological concentrations
of glucose became selectively enriched in ortho-tyrosine and
meta-tyrosine, implicating a hydroxyl radical-like species in
protein damage. Model system studies demonstrated that the
reaction pathway requires both a reactive carbonyl group and a
polyunsaturated fatty acid, involves lipid peroxidation, and
is blocked by the carbonyl scavenger aminoguanidine. To
explore the physiological relevance of the pathway, we used
mass spectrometry and HPLC to quantify oxidation products in
control and hyperglycemic rats. Hyperglycemia raised levels of
ortho-tyrosine, meta-tyrosine, and oxygenated lipids in the
retina, a tissue rich in polyunsaturated fatty acids. Rats
that received aminoguanidine also did not show this increase
in protein and lipid oxidation. In contrast, hyperlipidemia in
the absence of hyperglycemia failed to increase protein and
lipid oxidation products in the retina. Our observations
suggest that generation of a hydroxyl radical-like species by
a carbonyl/polyunsaturated fatty acid pathway might promote
localized oxidative stress in tissues vulnerable to diabetic
damage. This raises the possibility that antioxidant therapies
that specifically inhibit the pathway might delay the vascular
complications of diabetes.
PMID: 15855169 [PubMed - as supplied by publisher]
--------------------------------------------------------------
-------------------
Who loves ya. Tom Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore DEAD
PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking