Superoxide anion O2- is a member of the reactive oxgen species (ROS) and is a significant factor in inflammation, particularly in patients with inflamamatory joint disease. This radical is neutralized by the enzyme superoxide dismutase (SOD) that converts O2- into hydrogen peroxide (H2O2). However, if not transformed by this enzyme, the superoxide anion can react with NO to cause cartilage damage. SOD protects against the harmful effects of superoxide anion, and several SOD mimetics have been developed for reducing inflammation.
The concentrations of ROS are governed by the balance between the production of ROS and their elimination antioxidants such as vitamin E, Carotenoids, and bilirubin. SOD1 plays a key role in cell survival and growth, but overproduction of TNF-a inhibits the SOD1 antioxidant enzyme expression. SOD2 provides protection against ROS generated by hypoxia, and deficiency of SOD2 increases O2- in mitochondria. SOD3 protects cells agains O2- generated by neutrophils.
SOD mimetics decrease the inflammatory process by decreasing peroxynitrite formation leading to greater bioavailability of NO, decreased neutrophil sites of inflammation, and decreased release of proinflammatory cytokines. However, after reading all of the articles, it does seem as though TNF-a is by far the most important factor in alleviating inflammation of these diseases
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A combination of TNF-a inhibition along with antioxidant consumption sounds like one of the best treatments or prevention techniques
Eh, okay, to keep this short: H2O2 is safe? Greater than 30% concentrations of H2O2 are highly explosive and have been used for rocket fuel! Biologically, H2O2 can be safely dismutated into H2O and O2 by Catalase (which is really H2O2 dismutase), otherwise it either degrades spontaneously, through Fenton-like chemistry or the Haber-Weiss reaction to hydroxyl radical OH-, which is the most reactive ROS/RNS species commonly found. O2- and NO can combine to form HONOO/ONOO-, the formation of which is so fast it's diffusion-rate limited, but ONOO- damage is usually in the form of protein nitrosylation, whereas OH- has been associated with DNA damage and mitochondrial dysfunction leading to cell death. SOD1/2/3 protect cells with about the same affinity for O2-, the difference among them is in the cellular expression: MnSOD (SOD2) expression is mainly mitochondrial, and SOD2-/- are neonatally lethal. SOD1 and SOD3 knockouts have little to no phenotype (Liang and Patel, Free Radical Biology and Medicine, 2004). Superoxide itself, in the absence of excessive nitric oxide, is a fairly tame ROS; making lots of H2O2 is not necessarily better.
Sorry, forgot to add that while SOD catalyzed conversion of O2- to H2O2 is quite fast (10^8 or so), O2- will also spontaneously dismutate quite quickly without SOD, at about 10^4-10^5. H2O2 spontaneous dismutation happens so slowly that it is likely to be degreaded through another pathway first: likely GSH-mediated within a healthy cell, but forming OH- in a stressed cell.
What implications might this have for diet? You mentioned antioxidants including vitamin e and cartinoids, do you think that consuming more vitamin e may reduce oxygen radical mediated tissue destruction? Do you think that is valid on an organism sized scale? Are the super oxide dismutase and catalase enzymes found in many organisms dating back to prokaryotes, sufficient to control the destruction caused by this phenomenon? These aren't loaded questions, I am curious what your thoughts are.
So I thought that when levels of superoxides produced by a cell increases, the cell undergoes apoptosis? How does this play into the pathway of superoxide dismutase and in patients with inflammatory joint disease, what has cause these cells to be resistant to apoptosis? Does this disease predispose to cancer?
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