Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease

Simona Granata, Gianluigi Zaza, Simona Simone, Gaetano Villani, Dominga Latorre, Paola Pontrelli, Massimo Carella, Francesco Paolo Schena, Giuseppe Grandaliano, Giovanni Pertosa

Research output: Contribution to journalArticle

118 Citations (Scopus)

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.

Original languageEnglish
Article number388
JournalBMC Genomics
Volume10
DOIs
Publication statusPublished - Aug 21 2009

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Chronic Renal Insufficiency
Oxidative Stress
Healthy Volunteers
Oxidative Phosphorylation
Reactive Oxygen Species
Respiratory System
Genes
Renal Dialysis
Blood Cells
Western Blotting
Control Groups

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Granata, S., Zaza, G., Simone, S., Villani, G., Latorre, D., Pontrelli, P., ... Pertosa, G. (2009). Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease. BMC Genomics, 10, [388]. https://doi.org/10.1186/1471-2164-10-388

Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease. / Granata, Simona; Zaza, Gianluigi; Simone, Simona; Villani, Gaetano; Latorre, Dominga; Pontrelli, Paola; Carella, Massimo; Schena, Francesco Paolo; Grandaliano, Giuseppe; Pertosa, Giovanni.

In: BMC Genomics, Vol. 10, 388, 21.08.2009.

Research output: Contribution to journalArticle

Granata, S, Zaza, G, Simone, S, Villani, G, Latorre, D, Pontrelli, P, Carella, M, Schena, FP, Grandaliano, G & Pertosa, G 2009, 'Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease', BMC Genomics, vol. 10, 388. https://doi.org/10.1186/1471-2164-10-388
Granata S, Zaza G, Simone S, Villani G, Latorre D, Pontrelli P et al. Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease. BMC Genomics. 2009 Aug 21;10. 388. https://doi.org/10.1186/1471-2164-10-388
Granata, Simona ; Zaza, Gianluigi ; Simone, Simona ; Villani, Gaetano ; Latorre, Dominga ; Pontrelli, Paola ; Carella, Massimo ; Schena, Francesco Paolo ; Grandaliano, Giuseppe ; Pertosa, Giovanni. / Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease. In: BMC Genomics. 2009 ; Vol. 10.
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