title: Plasma protein carbonylation in chronic uremia.
abstract: BACKGROUND
  Carbonylation is an irreversible modification caused by the introduction into proteins of carbonyl derivatives (aldehydes and ketones), which can alter protein structure and function and lead to cellular dysfunction and tissue damage. Chronic uremia may be associated with an increased carbonyl overload ("carbonyl stress"), though carbonyl formation has been proposed so far for major plasma proteins only. In this study we looked for evidence and for the targets of plasma protein carbonylation in patients on hemodialysis. We also examined the effect of in vitro carbonylated albumin on mRNA levels of endothelial cell adhesion molecules involved in early atherogenesis.
  
  
  METHODS
  Carbonylated proteins in uremic plasma were detected by a covalent hydrazine bait strategy and identified by combining electrophoretic separation with mass spectrometry analysis of tryptic digests. Some plasma samples were first depleted of albumin and immunoglobulins to improve detection of lower abundance proteins. The functional impact of carbonylation was assessed in human vein endothelial cells by studying models of modified human serum albumin.
  
  
  RESULTS
  Post-dialysis plasma carbonylated protein levels were significantly increased compared to pre-dialysis levels. Susceptibility to carbonyl formation was described on a open-platform investigation for a number of plasma proteins, albumin being the main scavenger of carbonyl reactive species. Incubation of endothelial cells with low doses of carbonylated albumin caused a significant increase in intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 mRNA levels.
  
  
  CONCLUSIONS
  Chronic uremia appears as a state of "carbonyl stress" targeting several different plasma proteins. Carbonylated albumin displayed biological effects that may be relevant to uremic atherosclerosis.
authors: Aging Research Center, Ce.S.I., G. d'Annunzio University Foundation, Chieti-Pescara, Italy.
authors: Barbara
authors: B
authors: Pavone
authors: Vittorio
authors: V
authors: Sirolli
authors: Annalisa
authors: A
authors: Giardinelli
authors: Sonia
authors: S
authors: Bucci
authors: Federica
authors: F
authors: Forlì
authors: Moreno
authors: M
authors: Di Cesare
authors: Paolo
authors: P
authors: Sacchetta
authors: Natalia
authors: N
authors: Di Pietro
authors: Assunta
authors: A
authors: Pandolfi
authors: Andrea
authors: A
authors: Urbani
authors: Mario
authors: M
authors: Bonomini