Altered antioxidant capacity in human renal cell carcinoma: Role of glutathione associated enzymes

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• 作者：Marija Pljesa-Ercegovac ; Jasmina Mimic-Oka ; Dejan Dragicevic ; Ana Savic-Radojevic ; Marija Opacic ; Steva Pljesa ; Radoslav Radosavljevic ; Tatjana Simic
• 关键词：Antioxidant enzymes ; Glutathione ; Glutathione S-transferases ; Renal cell carcinoma
• 刊名：Urologic Oncology: Seminars and Original Investigations
• 出版年：2008
• 出版时间：March-April 2008
• 年：2008
• 卷：26
• 期：2
• 页码：175-181
• 全文大小：337 K

文摘

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 α and π expression was also explored.

Methods and materials

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, γ-glutamylcysteine synthetase (γ-GCS), γ-glutamyl transferase (γ-GT), and glutathione reductase (GR), as well as the activities of antioxidant enzymes glutathione peroxidase (GPX) and catalase (CAT) were determined spectrophotometrically. GST α and π 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, γ-GCS, is up-regulated (P < 0.001), while the activities of γ-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 α (P < 0.001) and unchanged GST π expression at the protein level.

Conclusions

Changes in redox status in RCC as a consequence of decreased enzyme antioxidant capacity, together with altered GST α expression, may be important factors in development and tumor growth. The up-regulation of γ-GCS and high levels of GSH in RCC may be an attempt to limit injury caused by oxidative stress.