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Overexpression of glyoxalase system enzymes in human kidney tumor
Cinzia Antognelli1, Francesca Baldracchini, Vincenzo Nicola Talesa
1University of Perugia, Department of Experimental Medicine, via Brunamonti, Perugia, Italy.
Purpose:
The purpose of this study was to investigate the messenger RNA expression and activity of glyoxalase I and glyoxalase II enzymes in a human renal carcinoma (clear cell adenocarcinoma) and in pair-matched normal tissue.
Patients And Methods:
Tumor and nontumor pair-matched specimens from the same organ were collected during radical nephrectomy from a group of 12 patients of both sexes. The mean age of the patients was 52.3 years (range, 50-60 years), and none of them had previously undergone neoadjuvant therapy. Gene expression and activity were measured by ribonuclease protection assay and current spectrophotometric methods, respectively. Intracellular levels of methylglyoxal were detected by high performance liquid chromatography.
Results:
A significant increase in the transcription levels of both glyoxalase I (about ninefold) and glyoxalase II (about threefold) was observed, compared with the pair-matched noncancerous tissues. Glyoxalase I activity was also higher in the pathological samples (about 2.5-fold) compared with the control samples and correlated with a significant decrease (about twofold) in methylglyoxal concentrations. At variance, glyoxalase II activity was significantly lower in pathological tissues than in the normal ones.
Discussion:
Our findings suggest a possible role of the glyoxalase system enzymes in the chemoresistance displayed by the kidney tumor. In fact, such a refractory behavior involves a decrease in the methylglyoxal level, a potent apoptosis activator. In addition, glyoxalase II activity decrease in the adenocarcinoma tissue suggests a likely role of the intermediate S-D-lactoylglutathione by supplying energy in actively proliferating cells. Finally, we point out a possible use of glyoxalase I inhibitors as anticancer drugs.
Insights
This study found increased glyoxalase I and II enzyme expression in kidney cancer, with higher glyoxalase I activity linked to lower methylglyoxal levels. These findings suggest potential roles in chemoresistance and new therapeutic targets.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- The glyoxalase system, comprising glyoxalase I and glyoxalase II, detoxifies reactive carbonyl species.
- Methylglyoxal is a reactive byproduct of metabolism that can induce apoptosis.
Purpose of the Study:
- To investigate messenger RNA (mRNA) expression and enzyme activity of glyoxalase I and glyoxalase II in human renal clear cell adenocarcinoma.
- To compare these parameters in tumor tissue versus matched normal renal tissue.
Main Methods:
- Pair-matched tumor and normal kidney specimens from 12 patients were analyzed.
- Gene expression was measured using ribonuclease protection assay.
- Enzyme activity was assessed spectrophotometrically, and methylglyoxal levels were quantified by high-performance liquid chromatography.
Main Results:
- Both glyoxalase I and glyoxalase II mRNA expression were significantly elevated in tumor tissues (approximately ninefold and threefold, respectively).
- Glyoxalase I activity was increased (2.5-fold) in tumors, correlating with a twofold decrease in methylglyoxal levels.
- Conversely, glyoxalase II activity was significantly lower in tumor tissues compared to normal tissues.
Conclusions:
- The glyoxalase system, particularly glyoxalase I, may play a role in kidney tumor chemoresistance by reducing methylglyoxal, an apoptosis inducer.
- Decreased glyoxalase II activity in adenocarcinoma suggests a role for its intermediate, S-D-lactoylglutathione, in providing energy for proliferating cancer cells.
- Glyoxalase I inhibitors show promise as potential anticancer drugs for renal carcinoma.