RGD Reference Report - Altered antioxidant capacity in human renal cell carcinoma: role of glutathione associated enzymes. - Rat Genome Database

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

Authors: Pljesa-Ercegovac, M  Mimic-Oka, J  Dragicevic, D  Savic-Radojevic, A  Opacic, M  Pljesa, S  Radosavljevic, R  Simic, T 
Citation: Pljesa-Ercegovac M, etal., Urol Oncol. 2008 Mar-Apr;26(2):175-81. doi: 10.1016/j.urolonc.2007.02.007. Epub 2007 Nov 26.
RGD ID: 7257550
Pubmed: PMID:18312938   (View Abstract at PubMed)
DOI: DOI:10.1016/j.urolonc.2007.02.007   (Journal Full-text)

PURPOSE: 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 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, 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal cell carcinoma  IEP 7257550protein:decreased expression:kidney:RGD 
renal cell carcinoma  ISOGSR (Homo sapiens)7257550; 7257550protein:decreased expression:kidney:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gsr  (glutathione-disulfide reductase)

Genes (Mus musculus)
Gsr  (glutathione reductase)

Genes (Homo sapiens)
GSR  (glutathione-disulfide reductase)


Additional Information