Importance of oxidatively modified proteins in chronic renal failure.
Considerable evidence has accumulated that chronic uremia is associated with a multifactorial immunoinflammatory syndrome, which occurs early in the course of renal failure, is accentuated with the progression of uremia, and culminates in maintenance dialysis therapy. We previously described the presence of a circulating oxidized plasma protein named advanced oxidation protein products (AOPPs). Beyond evidence that AOPPs represent an exquisite marker of oxidative stress, their role(s) in the pathophysiology of chronic renal failure and dialysis-related complications might be of great importance. Regarding the mechanisms of generation of AOPP, we underscore the importance of the chlorinated oxidants, previously solely considered as microbicidal agents, in the generation of AOPP. Indeed, AOPPs appear to act as true inflammatory mediators since they are able to trigger the oxidative burst in neutrophils as well as in monocytes. Thus, it is hypothesized that the AOPPs, which arise from the reaction between chlorinated oxidants and plasma proteins, constitute a new molecular basis for the deleterious activity of oxidants, and they could be considered to be true mediators of the proinflammatory effect of oxidative stress in uremia.
Descamps-Latscha
B
B
INSERM U507, Hôpital Necker, Paris, France. b.descamps@necker.fr
Witko-Sarsat
V
V
D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010586:Phagocytes / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D000975:Antioxidants; D015415:Biomarkers; D018836:Inflammation Mediators; D016877:Oxidants; D011506:Proteins