title: Hemodialysis induces p66(shc) gene expression in nondiabetic humans: correlations with oxidative stress and systemic inflammation.
abstract: OBJECTIVE
  Oxidative stress and inflammation characterize hemodialysis (HD) and are associated with malnutrition, cardiovascular disease, and poor clinical outcome. p66(shc) stimulates oxidative stress and atherogenesis. The objective of the present study was to assess p66(shc) expression levels in HD and their associations with inflammatory and oxidative stress markers.
  
  
  METHODS
  p66(shc) messenger ribonucleic acid (mRNA) was compared with systemic oxidative stress and inflammation markers in control subjects and patients on HD before and after a single HD session in a cross-sectional analysis.
  
  
  METHODS
  Outpatient hemodialysis unit.
  
  
  METHODS
  The study included stable HD patients (n = 21, men/women: 18/3) who were on HD 3 times per week for a minimum of 8 weeks; age-matched control subjects (n = 22, men/women:17/5).
  
  
  METHODS
  mRNA levels of p66(shc), tumor necrosis factor α (TNF-α), and pentraxin 3 (PTX3), p66(shc) protein levels in white blood cells, lipid peroxidation (in the form of plasma thiobarbituric acid-reactive substance [TBARS]) and serum C-reactive protein.
  
  
  RESULTS
  In patients on dialysis, of the p66(shc), TNF-α, and PTX3 mRNAs, p66(shc) protein levels were higher (P < .05) than in control subjects, as well as plasma TBARS and C-reactive protein (P < .05). p66(shc) mRNA directly correlated with TBARS (r = 0.69, P = .0005) and with TNF-α mRNA (r = 0.63, P = .003). These associations were confirmed in the whole study population (TBARS: r = 0.541, P = .0003; TNF-α: r = 0.581, P < .0001), whereas in the control group only the positive association between p66(shc) and TNF-α was detected. TNF-α was directly correlated with PTX3 both in HD patients (r = 0.72, P = .0005) and in the whole study group (r = 0.678, P < .0001). The dialysis session affected neither p66(shc) and TNF-α mRNA nor p66(shc) protein expression, whereas it further increased (P = .002) PTX3 mRNA. As compared with predialysis levels, TBARS were reduced (P < .05) after dialysis. In these conditions, p66(shc) remained directly correlated with TNF-α (r = 0.901, P < .0001).
  
  
  CONCLUSIONS
  Increased p66(shc) gene expression correlates with TNF-α mRNA and with levels of markers of oxidative stress in HD. We suggest a novel link between HD-associated inflammation and p66(shc) gene expression contributing to systemic oxidative stress.
authors: Clinica Medica Generale, DUC SMTT, Ospedale di Cattinara, Trieste, Italy. zanetti@units.it
authors: Michela
authors: M
authors: Zanetti
authors: Rocco
authors: R
authors: Barazzoni
authors: Gianluca
authors: G
authors: Gortan Cappellari
authors: Ismet
authors: I
authors: Burekovic
authors: Alessandra
authors: A
authors: Bosutti
authors: Alessia
authors: A
authors: Stocca
authors: Francesco
authors: F
authors: Bianco
authors: Marco
authors: M
authors: Ianche
authors: Giovanni
authors: G
authors: Panzetta
authors: Gianfranco
authors: G
authors: Guarnieri
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000097:blood; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D007962:Leukocytes; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000097:blood; D006435:Renal Dialysis; D000683:Serum Amyloid P-Component / Q000032:analysis; D055765:Shc Signaling Adaptor Proteins / Q000097:blood* / Q000235:genetics; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000099153:Pentraxins
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D012333:RNA, Messenger; D000683:Serum Amyloid P-Component; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins; C528024:SHC1 protein, human