Altered antioxidant capacity in human renal cell carcinoma: role of glutathione associated enzymes.
OBJECTIVE
We aimed to discern the role of glutathione (GSH) associated enzymes in maintaining high GSH levels in renal cell carcinoma (RCC) of the clear cell type and analyze RCC enzyme antioxidant capacity. Since changes in cellular redox balance in RCC might also be related to alterations of glutathione S-transferase (GST) phenotype, GST class alpha and pi expression was also explored.


METHODS
Human kidney specimens of tumor and distant nontumor regions were obtained from 15 patients with RCC at the time of surgery. The activities of GSH-replenishing enzymes, gamma-glutamylcysteine synthetase (gamma-GCS), gamma-glutamyl transferase (gamma-GT), and glutathione reductase (GR), as well as the activities of antioxidant enzymes glutathione peroxidase (GPX) and catalase (CAT) were determined spectrophotometrically. GST alpha and pi class expression was determined by immunoblot.


RESULTS
In the course of renal cancerization, significant changes appear in the activities of GSH-replenishing and antioxidant enzymes. The activity of the key enzyme of GSH synthesis, gamma-GCS, is up-regulated (P < 0.001), while the activities of gamma-GT and GR are down-regulated in renal tumors compared to nontumor tissue (P < 0.001 and P < 0.05, respectively). Activities of GPX and CAT were also down-regulated (P < 0.001 and P < 0.05, respectively) in RCC. Changes in enzyme antioxidant capacity in RCC were associated with decreased GST class alpha (P < 0.001) and unchanged GST pi expression at the protein level.


CONCLUSIONS
Changes in redox status in RCC as a consequence of decreased enzyme antioxidant capacity, together with altered GST alpha expression, may be important factors in development and tumor growth. The up-regulation of gamma-GCS and high levels of GSH in RCC may be an attempt to limit injury caused by oxidative stress.
Pljesa-Ercegovac
Marija
M
Institute of Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Mimic-Oka
Jasmina
J
Dragicevic
Dejan
D
Savic-Radojevic
Ana
A
Opacic
Marija
M
Pljesa
Steva
S
Radosavljevic
Radoslav
R
Simic
Tatjana
T
D000975:Antioxidants / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007680:Kidney Neoplasms / Q000201:enzymology*; D008875:Middle Aged; D010084:Oxidation-Reduction
D000975:Antioxidants; D005982:Glutathione Transferase