Upregulated glutathione transferase omega-1 correlates with progression of urinary bladder carcinoma

ABSTRACT

Objectives: Newly discovered glutathione transferase omega 1 (GSTO1-1) plays an important role in the glutathionylation cycle, a significant mechanism of protein function regulation. GSTO1-1 expression pattern has not been studied in transitional cell carcinoma (TCC), as yet.

Methods: A total of 56 TCC tumor and corresponding non-tumor specimens were investigated. Glutathione content and thioltransferase activity were measured spectrophotometrically. Protein-glutathione mixed disulfides were measured fluorimetrically. GSTO1-1 expression was determined by immunoblot and qPCR. Immunoprecipitation with GSTO1-1 antibody was followed by immunoblot using anti-GSTO1, GSTP1, c-Jun, JNK, Akt, phospho-Akt, and ASK1 antibody, while for the total S-glutathionylation levels non-reducing electrophoresis was performed.

Results: The contents of reduced glutathione and thioltransferase activity were significantly increased in tumor compared to non-tumor tissue. The increased GSTO1 expression in tumor tissue showed clear correlation with grade and stage. However, decreased total protein glutathionylation level in tumor compared to non-tumor samples was found. Immunoprecipitation has shown an association of GSTO1-1 with GSTP1, Akt, phospho-Akt, and ASK1 proteins.

Conclusions: GSTO1 deglutathionylase activity suggests its potential important role in redox perturbations present in TCC. Increased GSTO1-1 expression might contribute to TCC development and/or progression supporting the notion that GSTO1-1 may be a promising novel cancer target.

KEYWORDS:

• Glutathione transferase omega 1
• glutathione
• glutathionylation
• transitional cell carcinoma
• uroepithelium

Acknowledgements

We thank technician Mrs Sanja Sekulic for collecting data and support in the manuscript preparation.

Disclosure statements

No potential conflict of interest was reported by the authors.

ORCID

Tatjana Djukic http://orcid.org/0000-0003-1959-5115

Sonja Suvakov http://orcid.org/0000-0002-3743-1213

Additional information

Funding

This study was funded by the Serbian Ministry of Education, Science and Technological Development (grant number 175052).