title: Downregulation of nuclear-encoded genes of oxidative metabolism in dialyzed chronic kidney disease patients.
abstract: BACKGROUND
  Mitochondria, essential eukaryotic cells organelles defined as the "powerhouse of the cell" because of their ability to produce the vast majority of energy necessary for cellular metabolism, may have a primary role in the oxidative stress-related intracellular machinery associated to chronic kidney disease (CKD).
  
  
  METHODS
  To better assess this research assumption, we decided to study the key factors regulating mitochondrial oxidative metabolism in CKD patients in peritoneal dialysis (PD, n = 15) using several bio-molecular methodologies.
  
  
  RESULTS
  RT-PCR experiments demonstrate that the expression level of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear respiratory factor-1 (NRF-1), two genes primarily involved in mitochondrial biogenesis and functions, were significantly hypo-expressed in peripheral blood mononuclear cells of PD patients compared to healthy subjects (HS, n = 15). Additionally, mRNA levels of several PGC1-α downstream target genes (TFAM, COX6C,COX7C, UQCRH and MCAD) were profoundly down-regulated in PD cells. TFAM protein analysis confirmed gene-expression results. High plasmatic concentration of Malondialdehyde found in PD patients, confirmed the contribution of the oxidative stress to these biological effects. Finally, Nuclear factor erythroid-derived 2-like 2 (NRF2 or NFE2L2), a transcription factor for numerous antioxidant/detoxifying enzymes and one of its target genes, superoxide dismutase-2 mitochondrial (SOD2) were up-regulated in PD compared to HS.
  
  
  CONCLUSIONS
  Our results revealed, for the first time, that CKD-PD patients' PBMC, through a complex intracellular biochemical machinery, are able to modulate their mitochondrial functions probably in the attempt to reduce oxidative metabolic damage and to turn on a valuable defense cellular strategy against oxidative stress.
authors.affiliation: Renal Unit, Department of Medicine, University-Hospital of Verona, Verona, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zaza
authors.forename: Simona
authors.initials: S
authors.lastname: Granata
authors.forename: Valentina
authors.initials: V
authors.lastname: Masola
authors.forename: Carlo
authors.initials: C
authors.lastname: Rugiu
authors.forename: Francesco
authors.initials: F
authors.lastname: Fantin
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Schena
authors.forename: Antonio
authors.initials: A
authors.lastname: Lupo
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D014157:Transcription Factors