Oxidative Stress In Lupus
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From: ironjustice on 22 Jul 2008 07:05 "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] -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
From: ironjustice on 22 Jul 2008 14:41 On Jul 22, 4:05 am, ironjustice <teamtan...(a)hotmail.com> wrote:On Jul 22, 4:05 am, ironjustice <teamtan...(a)hotmail.com> wrote:catalase oxidatively modified << "Catalase is oxidatively modified among SLE patients" "The target of modification was due to oxidative stress" "Phytic acid and catalase each attenuated A549 cell DNA damage" Looks like my free bisphosphonate steps up to .. stand in .. again. Catalase and phytic acid do the **same thing** in the body. Catalase is **shown** to BE "modified oxidatively" IN those with SLE. One might think phytic acid would be considered in lupus. It could replace / standin for that which catalase is incapable of accomplishing. DUE TO the oxidative modification inflicted upon catalase .. That's using logic and reason and science. Phytic acid is found in your plants. It is a free bisphosphonate found in your grub .. http://tinyurl.com/2wuhuk They / catalase and / or phytic acid do the same thing. http://tinyurl.com/6qqefj Original Contributions Cigarette smoke augments asbestos-induced alveolar epithelial cell injury: role of free radicals David W. Kamp, , *, c, Marc J. Greenberger*, c, Jane S. Sbalchierro*, b, c, Scott E. Preusen*, c and Sigmund A. Weitzmanb, c * Division of Pulmonary Medicine, Northwestern University Medical School, Chicago, IL, USA Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
From: ironjustice on 22 Jul 2008 21:05 On Jul 22, 1:12 pm, aka_velcro <Crystalarev...(a)gmail.com> wrote:snip << Remember do not break crush chew or inject those meds. Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
From: Chuck on 23 Jul 2008 05:11 Wow, oxidative stress plays a role in pathological damage. What a revelation! Whodathunkit Arealshocka
From: Michael B on 23 Jul 2008 06:15
The wonderful thing is that OUR TOM was the one to bring this fact to the attention of the medical community. Isn't that great? And a real medical doctor, Dr Denham Harman, blatantly plagiarized the information and made it look like it was his idea. Ooops, no, wait. He made that observation in 1957. Maybe it was his idea after all. On Jul 23, 5:11 am, Chuck <ShorThi...(a)aol.com> wrote: > Wow, oxidative stress plays a role in pathological damage. What a > revelation! Whodathunkit Arealshocka |