Nuclear Respiratory Factor-1 (NRF-1) Gene Expression in Chronic Kidney Disease Patients Undergoing Hemodialysis and Mitochondrial Oxidative Dysregulation.
BACKGROUND
Chronic kidney disease (CKD) is characterized by progressive irreversible deterioration of renal functions. Advanced stages of CKD are associated with oxidative stress due to the imbalance between oxidant production and antioxidant defense mechanisms. Survival of patients with end stage renal diseases is maintained on variable forms of renal replacement therapies (RRT) which include peritoneal dialysis, hemodialysis, and sometimes renal transplantation. In humans, Nuclear Respiratory Factor 1 (NRF-1) gene encodes for a transcription factor that, together with the transcriptional co-activator encoded by Peroxisome Proliferator activated Receptor Gamma coactivator 1 Alpha (PGC1-a) gene, stimulates the expression of a broad set of nuclear genes (as COX6C) which are involved in mitochondrial biogenesis and functions. As mitochondria are considered a major source of reactive oxidant species, the objective of the present study was to assess mitochondrial oxidative dysregulation occurring in chronic kidney disease patients undergoing hemodialysis employing NRF-1 and COX6C genes' expression as an indicator of mitochondrial oxidative metabolism.


METHODS
Forty-nine chronic kidney disease patients undergoing intermittent hemodialysis were included in the present study. A group of thirty-three age- and gender- matched healthy volunteers served as a control group. Assessment of expression of NRF-1 and COX6C genes was performed using quantitative real-time PCR technique.


RESULTS
NRF-1 and COX6C expression showed a statistically significant difference between both studied groups being down-regulated in CKD patients. In addition, malondialdehyde (MDA) levels were higher in patients on hemodialysis indicating lipid peroxidation. A negative correlation was detected between MDA level and expression of both NRF-1 and COX6C genes.


CONCLUSIONS
Chronic kidney disease patients undergoing hemodialysis might be subjected to potential mitochondrial oxidative dysregulation with subsequent possible vascular and tissue injury.
Doaa
D
Hashad
Iman
I
Elgohry
Fatma
F
Dwedar
D000328:Adult; D016022:Case-Control Studies; D015536:Down-Regulation; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D016896:Treatment Outcome
C404795:COX6c protein, human; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; D008315:Malondialdehyde; D003576:Electron Transport Complex IV