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From: ironjustice on 24 Jul 2008 17:55
On Jul 24, 12:12 pm, "Paul T. Holland" <pholl...(a)bellatlantic.net>
wrote: long windeded whack <<

http://kook.us/holland.htm

"Oxidative stress damage in systemic lupus erythematosus "
"Premature onset of atherogenesis"

Detection of Catalase as a major protein target of the lipid
peroxidation product 4-HNE and the lack of its genetic association as
a risk factor in SLE.
D'Souza A, Kurien BT, Rodgers R, Shenoi J, Kurono S, Matsumoto H,
Hensley K, Nath SK, Scofield RH


BMC Med Genet 2008 Jul 7; 9(1):62.


ABSTRACT:
BACKGROUND: Systemic lupus erythematosus (SLE) is a multifactorial
disorder characterized by the presence of autoantibodies. We and
others have implicated free radical mediated peroxidative damage in
the pathogenesis of SLE. Since harmful free radical products are
formed during this oxidative process, including 4-Hydroxy 2-nonenol
(4-
HNE) and malondialdehyde (MDA), we hypothesized that specific HNE-
protein adducts would be present in SLE red blood cell (RBC)
membranes. Catalase is located on chromosome 11p13 where linkage
analysis has revealed a marker in the same region of the genome among
families with thrombocytopenia, a clinical manifestation associated
with severe lupus in SLE affected pedigrees. Moreover, SLE afflicts
African-Americans three times more frequently than their European
American counterparts. Hence we investigated the effects of a genetic
polymorphism of catalase on risk and severity of SLE in 48 pedigrees
with African American ancestry.
METHODS: Tryptic digestion followed by matrix assisted laser
desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS)
analysis was used to identify the protein(s) modified by HNE,
following Coomassie staining to visualize the bands on the acrylamide
gels. Genotyping analysis for the Ci T, -262bp polymorphism in the
promoter region of catalase was performed by PCR-RFLP and direct PCR-
sequencing. We used a apedigree disequilibrium testa for the family
based association analysis, implemented in the PDT program to analyze
the genotyping results.
RESULTS: We found two proteins to be HNE-modified, migrating around
80
and 50 kD respectively. Tryptic digestion followed by matrix assisted
laser desorption/ionization time-of-flight mass spectrometry (MALDI-
TOFMS) analysis of the Coomassie stained 80 kD band revealed that the
target of HNE modification was catalase, a protein shown to associate
with RBC membrane proteins. All the test statistics carried out on
the
genotyping analysis for the Ci T, -262bp polymorphism in the promoter
region of catalase were non-significant (p>0.05) in our data, which
suggested that this SNP is not associated with SLE.
CONCLUSION: Our results indicate that catalase is one of the proteins
modified due to oxidative stress. However, catalase may not be a
susceptibility gene for SLE. Nonetheless, catalase is oxidatively
modified among SLE patients. This suggests a possible role between
oxidative modification of catalase and its affects on enzymatic
activity in SLE. An oxidatively modified catalase could be one of the
reasons for lower enzymatic activity among SLE subjects, which in
turn
could favor the accumulation of deleterious hydrogen peroxide.
Furthermore, HNE-products are potential neoantigens and could be
involved in the pathogenesis of SLE. Decrease in catalase activity
could affect the oxidant-antioxidant balance. Chronic disturbance of
this balance in patients with SLE may work favorably for the
premature
onset of atherogenesis with severe vascular effect.


BMC medical genetics [BMC Med Genet]


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