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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-1?) 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-? 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.

SUBMITTER: Zaza G 

PROVIDER: S-EPMC3810143 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Downregulation of nuclear-encoded genes of oxidative metabolism in dialyzed chronic kidney disease patients.

Zaza Gianluigi G   Granata Simona S   Masola Valentina V   Rugiu Carlo C   Fantin Francesco F   Gesualdo Loreto L   Schena Francesco Paolo FP   Lupo Antonio A  

PloS one 20131028 10


<h4>Background</h4>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).<h4>Methods</h4>To better assess this research assumption, we decided to study the key factors regulating mitochondrial oxidative metabolism in CKD patients in periton  ...[more]

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