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Logo of bmcgenoBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Genomics
 
BMC Genomics. 2009; 10: 388.
Published online Aug 21, 2009. doi:  10.1186/1471-2164-10-388
PMCID: PMC2737002
Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease
Simona Granata,#1 Gianluigi Zaza,corresponding author#1 Simona Simone,1 Gaetano Villani,2 Dominga Latorre,2 Paola Pontrelli,3 Massimo Carella,4 Francesco Paolo Schena,1 Giuseppe Grandaliano,1 and Giovanni Pertosa1
1Renal, Dialysis and Transplant Unit-Department of Emergency and Transplantation, University of Bari, Italy
2Department of Medical Biochemistry, Biology & Physics, University of Bari, Italy
3Department of Biomedical Sciences, University of Foggia, Foggia, Italy
4Medical Genetics Service, "Casa Sollievo della Sofferenza", Hospital, IRCCS, San Giovanni Rotondo, Italy
corresponding authorCorresponding author.
#Contributed equally.
Simona Granata: simonagranata79/at/yahoo.it; Gianluigi Zaza: g.zaza/at/nephro.uniba.it; Simona Simone: simonasimone1976/at/libero.it; Gaetano Villani: villani/at/biochem.uniba.it; Dominga Latorre: dominga.latorre/at/libero.it; Paola Pontrelli: paolapontre/at/libero.it; Massimo Carella: m.carella/at/operapadrepio.it; Francesco Paolo Schena: fp.schena/at/nephro.uniba.it; Giuseppe Grandaliano: g.grandaliano/at/nephro.uniba.it; Giovanni Pertosa: g.pertosa/at/nephro.uniba.it
Received March 24, 2009; Accepted August 21, 2009.
Abstract
Background
Chronic renal disease (CKD) is characterized by complex changes in cell metabolism leading to an increased production of oxygen radicals, that, in turn has been suggested to play a key role in numerous clinical complications of this pathological condition. Several reports have focused on the identification of biological elements involved in the development of systemic biochemical alterations in CKD, but this abundant literature results fragmented and not exhaustive.
Results
To better define the cellular machinery associated to this condition, we employed a high-throughput genomic approach based on a whole transcriptomic analysis associated with classical molecular methodologies. The genomic screening of peripheral blood mononuclear cells revealed that 44 genes were up-regulated in both CKD patients in conservative treatment (CKD, n = 9) and hemodialysis (HD, n = 17) compared to healthy subjects (HS, n = 8) (p < 0.001, FDR = 1%). Functional analysis demonstrated that 11/44 genes were involved in the oxidative phosphorylation system. Western blotting for COXI and COXIV, key constituents of the complex IV of oxidative phosphorylation system, performed on an independent testing-group (12 healthy subjects, 10 CKD and 14 HD) confirmed an higher synthesis of these subunits in CKD/HD patients compared to the control group. Only for COXI, the comparison between CKD and healthy subjects reached the statistical significance. However, complex IV activity was significantly reduced in CKD/HD patients compared to healthy subjects (p < 0.01). Finally, CKD/HD patients presented higher reactive oxygen species and 8-hydroxydeoxyguanosine levels compared to controls.
Conclusion
Taken together these results suggest, for the first time, that CKD/HD patients may have an impaired mitochondrial respiratory system and this condition may be both the consequence and the cause of an enhanced oxidative stress.
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