mRNA Study on Cu/Zn Superoxide Dismutase Induction by Hemodialysis Treatment

Abstract

Background/Aims: There is little or no controversy about the increased oxidative stress of hemodialysis (HD) patients. Several reports show that the activity of superoxide dismutase (SOD), one of the major endogenous antioxidant enzymes, in plasma is elevated among HD patients. It is still unclear, however, whether this elevation is due to the promotion of SOD production or a decrease in renal excretion of SOD. This study was designed to investigate the cause of the SOD activation in HD patients, and we examined the expression of SOD mRNA levels in leukocytes of patients with chronic renal failure. Methods: The total plasma SOD activity was determined by the nitroblue tetrazolium method, plasma SOD contents by ELISA, and SOD mRNA levels in leukocytes by RT-PCR. Results: Our results demonstrated that contents and mRNA levels of Cu/Zn SOD in HD patients are 4.4 times and 2.0 times, respectively, as large as those in healthy controls. Furthermore, in contrast to nondialyzed chronic renal failure patients, we observed higher concentrations of Cu/Zn SOD in plasma and a more enhanced mRNA expression of Cu/Zn SOD in leukocytes of HD patients. Conclusion: Increased Cu/Zn SOD mRNA reflects enhanced antioxidant capacity of leukocytes and can be a promising oxidative stress marker in HD patients.

Comparison of Effect of Vitamin E-Coated Dialyzer and Oral Vitamin E on Hemodialysis-Induced Cu/Zn-Superoxide Dismutase

“…Noteworthy enough, we found a 2.0-fold increase of Cu/Zn-SOD mRNA in leukocytes in hemodialysis patients as compared with the same in healthy controls. Also we found 1.7-fold increase of Cu/Zn-SOD mRNA in hemodialysis patients as compared with the same in non-dialyzed CRF patients [14]. We speculate this finding is probably due to the direct contact of leukocytes with dialyzer membrane.…”

“…VE-PO resulted in a progressive decrease in Cu/Zn-SOD content (from 3.0 ± 1.6 to 0.6 ± 0.6; p < 0.01), which reached the level of non-dialyzed CRF patients by 6 months [14]. Similarly, a concomitant progressive decrease was observed in VE-BMD (from 3.6 ± 1.6 to 0.7 ± 0.4; p < 0.01), suggesting an associated diminution in oxidative stress.…”

“…We speculate that those organs such as the liver and kidneys where ROM in the lipid of leukocytes membrane were carried by the blood circulation during hemodialysis would in turn facilitate Cu/Zn-SOD production, resulting in the elevation of plasma Cu/Zn-SOD content level. In addition, we had reported elevation of total SOD activity [13] and Cu/Zn-SOD content, whereas Mn-SOD content did not change significantly in hemodialysis patients [14]. Therefore, we believe it would be reasonable to assume that Cu/Zn-SOD content and its mRNA can be a characteristic measure of oxidative stress caused by hemodialysis.…”

Significance of Cu/Zn-Superoxide Dismutase Levels in Hemodialysis Patients: A Mini Review

“…Moreover, Akiyama et al reported that Cu/Zn-SOD mRNA levels were also high in the white blood cells of these patients, thus leading to increased Cu/Zn-SOD production [12]. On the other hand, Futenma et al examined Cu/Zn-SOD isomers using gel column chromatography and revealed that despite a decrease in tetramers or octamers of Cu/Zn-SOD, there was a marked increase in Cu/Zn-SOD levels in hemodialysis patients owing to an increase in monomers of Cu/ Zn-SOD that are immunologically active but enzymatically inactive [26].…”

Effect of Hydrogen Peroxide and High Glucose on the Glucose Metabolism of Lymphoma-derived U937 Cells

“…We previously reported increased Cu / Zn-superoxide dismutase SOD in the blood and upregulated Cu / Zn-SOD mRNA in the leukocytes of hemodialysis patients, as well as a correlation between leukocyte membrane lipid peroxidation and expression of Cu / Zn-SOD mRNA in hemodialysis patients ; this causes oxidative stress which may also occur due to blood cell contact with the dialysis membrane 7,8 . Dialysis-associated oxidative stress is in response to depletion of the intracellular ATP supply, shifting to other intracellular glucose metabolic pathways, such as the polyol pathway from the glycolytic system, hexosamine pathway, pentose phosphate pathway, and protein kinase C pathway 12,13 , however many aspects of this shift are not well defined.…”