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Marija Matic
Institute of Medical and Clinical Biochemistry, 11000 Belgrade, Serbia

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Journal article
Published: 17 December 2019 in Cancers
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Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis.

ACS Style

Tanja Radic; Vesna Coric; Zoran Bukumiric; Marija Pljesa-Ercegovac; Tatjana Djukic; Natasa Avramovic; Marija Matic; Smiljana Mihailovic; Dejan Dragicevic; Zoran Dzamic; Tatjana Simic; Ana Savic-Radojevic. GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients. Cancers 2019, 11, 2038 .

AMA Style

Tanja Radic, Vesna Coric, Zoran Bukumiric, Marija Pljesa-Ercegovac, Tatjana Djukic, Natasa Avramovic, Marija Matic, Smiljana Mihailovic, Dejan Dragicevic, Zoran Dzamic, Tatjana Simic, Ana Savic-Radojevic. GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients. Cancers. 2019; 11 (12):2038.

Chicago/Turabian Style

Tanja Radic; Vesna Coric; Zoran Bukumiric; Marija Pljesa-Ercegovac; Tatjana Djukic; Natasa Avramovic; Marija Matic; Smiljana Mihailovic; Dejan Dragicevic; Zoran Dzamic; Tatjana Simic; Ana Savic-Radojevic. 2019. "GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients." Cancers 11, no. 12: 2038.

Journal article
Published: 03 August 2019 in Medicina
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Background and Objectives: Experimental data show that superoxide dismutase 2 (SOD2) is involved in ochratoxin (OTA)-induced nephrotoxicity, whereas clinical data indicate the role of SOD2 rs4880 or glutathione peroxidase 1 (GPX1) rs1050450 polymorphisms in end-stage renal disease and urothelial carcinoma risk, known to be the major complications of Balkan endemic nephropathy (BEN). Therefore, we hypothesized that SOD2 and GPX1 gene polymorphisms would influence the risk of BEN and its associated tumors. Materials and Methods: The study was conducted in 207 BEN patients and 86 controls from endemic areas. Results: Individuals with both copies of variant SOD2 allele, known for lower mitochondrial antioxidant protection, are at a significantly higher BEN risk (OR = 2.6, p = 0.021). No association was observed between GPX1 gene polymorphism and BEN risk. Combining SOD2 and GPX1 genotypes did not alter the risk of BEN development. Regarding the risk of urothelial tumors in BEN patients, none of the polymorphisms studied was significantly associated with the risk of these tumors. Conclusions: Polymorphism in SOD2 rs4880 gene affects the risk of BEN development. Hence, SOD2 genotyping could, together with a panel of other enzymes, be used as a biomarker of susceptibility in BEN areas.

ACS Style

Biljana Dragicevic; Sonja Suvakov; Djurdja Jerotic; Zorica Reljic; Ljubica Djukanovic; Ivanka Zelen; Marija Pljesa-Ercegovac; Ana Savic-Radojevic; Tatjana Simic; Dejan Dragicevic; Marija Matic. Association of SOD2 (rs4880) and GPX1 (rs1050450) Gene Polymorphisms with Risk of Balkan Endemic Nephropathy and its Related Tumors. Medicina 2019, 55, 435 .

AMA Style

Biljana Dragicevic, Sonja Suvakov, Djurdja Jerotic, Zorica Reljic, Ljubica Djukanovic, Ivanka Zelen, Marija Pljesa-Ercegovac, Ana Savic-Radojevic, Tatjana Simic, Dejan Dragicevic, Marija Matic. Association of SOD2 (rs4880) and GPX1 (rs1050450) Gene Polymorphisms with Risk of Balkan Endemic Nephropathy and its Related Tumors. Medicina. 2019; 55 (8):435.

Chicago/Turabian Style

Biljana Dragicevic; Sonja Suvakov; Djurdja Jerotic; Zorica Reljic; Ljubica Djukanovic; Ivanka Zelen; Marija Pljesa-Ercegovac; Ana Savic-Radojevic; Tatjana Simic; Dejan Dragicevic; Marija Matic. 2019. "Association of SOD2 (rs4880) and GPX1 (rs1050450) Gene Polymorphisms with Risk of Balkan Endemic Nephropathy and its Related Tumors." Medicina 55, no. 8: 435.

Journal article
Published: 23 July 2019 in Toxins
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The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (GSTM1) deletion polymorphism, was further analyzed. Polymorphisms in Nrf2 (rs6721961), SOD2 (rs4880), GPX1 (rs1050450), and GSTM1 were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The SOD2 Val/Val genotype increased ESRD risk (OR = 2.01, p = 0.002), which was even higher in combination with the GPX1 Leu/Leu genotype (OR = 3.27, p = 0.019). Polymorphism in SOD2 also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the Nrf2 (C/C) and GPX1 (Leu/Leu) genotypes in addition to a patients’ age and GSTM1 polymorphism. Similarly, the GPX1 (Leu/Leu) genotype contributed to longer cardiovascular survival. Conclusions: Our results show that SOD2, GPX1, and Nrf2 polymorphisms are associated with ESRD development and can predict survival.

ACS Style

Djurdja Jerotic; Marija Matic; Sonja Suvakov; Katarina Vucicevic; Tatjana Damjanovic; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Vesna Coric; Aleksandra Stefanovic; Jasmina Ivanisevic; Zorana Jelic-Ivanovic; Lana McClements; Nada Dimkovic; Tatjana Simic. Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients. Toxins 2019, 11, 431 .

AMA Style

Djurdja Jerotic, Marija Matic, Sonja Suvakov, Katarina Vucicevic, Tatjana Damjanovic, Ana Savic-Radojevic, Marija Pljesa-Ercegovac, Vesna Coric, Aleksandra Stefanovic, Jasmina Ivanisevic, Zorana Jelic-Ivanovic, Lana McClements, Nada Dimkovic, Tatjana Simic. Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients. Toxins. 2019; 11 (7):431.

Chicago/Turabian Style

Djurdja Jerotic; Marija Matic; Sonja Suvakov; Katarina Vucicevic; Tatjana Damjanovic; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Vesna Coric; Aleksandra Stefanovic; Jasmina Ivanisevic; Zorana Jelic-Ivanovic; Lana McClements; Nada Dimkovic; Tatjana Simic. 2019. "Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients." Toxins 11, no. 7: 431.

Review
Published: 28 November 2018 in International Journal of Molecular Sciences
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Multifunctional enzymes glutathione transferases (GSTs) are involved in the development of chemoresistance, thus representing a promising target for a novel approach in cancer treatment. This superfamily of polymorphic enzymes exhibits extraordinary substrate promiscuity responsible for detoxification of numerous conventional chemotherapeutics, at the same time regulating signaling pathways involved in cell proliferation and apoptosis. In addition to upregulated GST expression, different cancer cell types have a unique GST signature, enabling targeted selectivity for isoenzyme specific inhibitors and pro-drugs. As a result of extensive research, certain GST inhibitors are already tested in clinical trials. Catalytic properties of GST isoenzymes are also exploited in bio-activation of specific pro-drugs, enabling their targeted accumulation in cancer cells with upregulated expression of the appropriate GST isoenzyme. Moreover, the latest approach to increase specificity in treatment of solid tumors is development of GST pro-drugs that are derivatives of conventional anti-cancer drugs. A future perspective is based on the design of new drugs, which would selectively target GST overexpressing cancers more prone to developing chemoresistance, while decreasing side effects in off-target cells.

ACS Style

Marija Pljesa-Ercegovac; Ana Savic-Radojevic; Marija Matic; Vesna Coric; Tatjana Djukic; Tanja Radic; Tatjana Simic. Glutathione Transferases: Potential Targets to Overcome Chemoresistance in Solid Tumors. International Journal of Molecular Sciences 2018, 19, 3785 .

AMA Style

Marija Pljesa-Ercegovac, Ana Savic-Radojevic, Marija Matic, Vesna Coric, Tatjana Djukic, Tanja Radic, Tatjana Simic. Glutathione Transferases: Potential Targets to Overcome Chemoresistance in Solid Tumors. International Journal of Molecular Sciences. 2018; 19 (12):3785.

Chicago/Turabian Style

Marija Pljesa-Ercegovac; Ana Savic-Radojevic; Marija Matic; Vesna Coric; Tatjana Djukic; Tanja Radic; Tatjana Simic. 2018. "Glutathione Transferases: Potential Targets to Overcome Chemoresistance in Solid Tumors." International Journal of Molecular Sciences 19, no. 12: 3785.

Journal article
Published: 01 January 2018 in The Tohoku Journal of Experimental Medicine
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Glutathione S-transferases (GSTs), a superfamily of multifunctional enzymes, play an important role in the onset and progression of renal cell carcinoma (RCC). However, novel GST omega class (GSTO), consisting of GSTO1-1 and GSTO2-2 isoenzymes, has not been studied in RCC yet. Two coding single nucleotide polymorphisms (SNPs) supposedly affect their functions: GSTO1*C419A (rs4925) causing alanine to aspartate substitution (*A140D) and GSTO2*A424G (rs156697) causing asparagine to aspartate substitution (*N142D), and have been associated with several neurodegenerative diseases and cancers. Functional relevance of yet another GSTO2 polymorphism, identified at the 5′ untranslated (5′UTR) gene region (GSTO2*A183G, rs2297235), has not been clearly discerned so far. Therefore, we aimed to assess the effect of specific GSTO1 and GSTO2 gene variants, independently and in interaction with established risk factors (smoking, obesity and hypertension) on the risk for the most aggressive RCC subtype, the clear cell RCC (ccRCC). Genotyping was performed in 239 ccRCC patients and 350 matched controls, while plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were determined by ELISA. As a result, combined effect of all three variant genotypes exhibited almost 3-fold risk of RCC development. Additionally, this association was confirmed at the haplotype level [variant GSTO1*A/GSTO2*G (rs156697)/GSTO2*G (rs2297235) haplotype], suggesting a potential role of those variants in propensity to RCC. Regarding the gene-environment interactions, variant GSTO2*G (rs156697) homozygous smokers are at higher ccRCC risk. Association in terms of oxidative DNA damage was found for GSTO2 polymorphism in 5′UTR and 8-OHdG. In conclusion, the concomitance of GSTO polymorphisms may influence ccRCC risk.

ACS Style

Tanja M. Radic; Vesna M. Coric; Marija S. Pljesa-Ercegovac; Gordana M. Basta-Jovanovic; Sanja M. Radojevic-Skodric; Dejan P. Dragicevic; Marija G. Matic; Ljiljana M. Bogdanovic; Zoran M. Dzamic; Tatjana P. Simic; Ana R. Savic-Radojevic. Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is Associated with Risk of Clear Cell Renal Cell Carcinoma. The Tohoku Journal of Experimental Medicine 2018, 246, 35 -44.

AMA Style

Tanja M. Radic, Vesna M. Coric, Marija S. Pljesa-Ercegovac, Gordana M. Basta-Jovanovic, Sanja M. Radojevic-Skodric, Dejan P. Dragicevic, Marija G. Matic, Ljiljana M. Bogdanovic, Zoran M. Dzamic, Tatjana P. Simic, Ana R. Savic-Radojevic. Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is Associated with Risk of Clear Cell Renal Cell Carcinoma. The Tohoku Journal of Experimental Medicine. 2018; 246 (1):35-44.

Chicago/Turabian Style

Tanja M. Radic; Vesna M. Coric; Marija S. Pljesa-Ercegovac; Gordana M. Basta-Jovanovic; Sanja M. Radojevic-Skodric; Dejan P. Dragicevic; Marija G. Matic; Ljiljana M. Bogdanovic; Zoran M. Dzamic; Tatjana P. Simic; Ana R. Savic-Radojevic. 2018. "Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is Associated with Risk of Clear Cell Renal Cell Carcinoma." The Tohoku Journal of Experimental Medicine 246, no. 1: 35-44.

Journal article
Published: 13 March 2017 in Redox Report
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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. 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. 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. 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.

ACS Style

Tatjana Djukic; Tatjana Simic; Marija Pljesa-Ercegovac; Marija Matic; Sonja Suvakov; Vesna Coric; Dejan Dragicevic; Ana Savic-Radojevic. Upregulated glutathione transferase omega-1 correlates with progression of urinary bladder carcinoma. Redox Report 2017, 22, 486 -492.

AMA Style

Tatjana Djukic, Tatjana Simic, Marija Pljesa-Ercegovac, Marija Matic, Sonja Suvakov, Vesna Coric, Dejan Dragicevic, Ana Savic-Radojevic. Upregulated glutathione transferase omega-1 correlates with progression of urinary bladder carcinoma. Redox Report. 2017; 22 (6):486-492.

Chicago/Turabian Style

Tatjana Djukic; Tatjana Simic; Marija Pljesa-Ercegovac; Marija Matic; Sonja Suvakov; Vesna Coric; Dejan Dragicevic; Ana Savic-Radojevic. 2017. "Upregulated glutathione transferase omega-1 correlates with progression of urinary bladder carcinoma." Redox Report 22, no. 6: 486-492.

Journal article
Published: 01 July 2016 in Free Radical Biology and Medicine
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ACS Style

Vesna M. Coric; Tatjana P. Simic; Tatjana D. Pekmezovic; Gordana M. Basta-Jovanovic; Ana R. Savic Radojevic; Sanja M. Radojevic-Skodric; Marija G. Matic; Dejan P. Dragicevic; Tanja M. Radic; Zoran M. Dzamic; Marija S. Pljesa-Ercegovac. The association of GSTM1 genotype with the risk of renal cell carcinoma development and prognosis. Free Radical Biology and Medicine 2016, 96, 1 .

AMA Style

Vesna M. Coric, Tatjana P. Simic, Tatjana D. Pekmezovic, Gordana M. Basta-Jovanovic, Ana R. Savic Radojevic, Sanja M. Radojevic-Skodric, Marija G. Matic, Dejan P. Dragicevic, Tanja M. Radic, Zoran M. Dzamic, Marija S. Pljesa-Ercegovac. The association of GSTM1 genotype with the risk of renal cell carcinoma development and prognosis. Free Radical Biology and Medicine. 2016; 96 ():1.

Chicago/Turabian Style

Vesna M. Coric; Tatjana P. Simic; Tatjana D. Pekmezovic; Gordana M. Basta-Jovanovic; Ana R. Savic Radojevic; Sanja M. Radojevic-Skodric; Marija G. Matic; Dejan P. Dragicevic; Tanja M. Radic; Zoran M. Dzamic; Marija S. Pljesa-Ercegovac. 2016. "The association of GSTM1 genotype with the risk of renal cell carcinoma development and prognosis." Free Radical Biology and Medicine 96, no. : 1.

Journal article
Published: 01 July 2016 in Free Radical Biology and Medicine
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ACS Style

Tatjana Djukic; Sonja Suvakov; Miroslav Stamenkovic; Ivan Sencanic; Jelena Smiljic; Marija Pljesa-Ercegovac; Marija Matic; Tatjana Simic; Ana Savic-Radojevic. Association of glutathione S-transferases M1 and T1 polymorphisms with glaucoma. Free Radical Biology and Medicine 2016, 96, 1 .

AMA Style

Tatjana Djukic, Sonja Suvakov, Miroslav Stamenkovic, Ivan Sencanic, Jelena Smiljic, Marija Pljesa-Ercegovac, Marija Matic, Tatjana Simic, Ana Savic-Radojevic. Association of glutathione S-transferases M1 and T1 polymorphisms with glaucoma. Free Radical Biology and Medicine. 2016; 96 ():1.

Chicago/Turabian Style

Tatjana Djukic; Sonja Suvakov; Miroslav Stamenkovic; Ivan Sencanic; Jelena Smiljic; Marija Pljesa-Ercegovac; Marija Matic; Tatjana Simic; Ana Savic-Radojevic. 2016. "Association of glutathione S-transferases M1 and T1 polymorphisms with glaucoma." Free Radical Biology and Medicine 96, no. : 1.

Journal article
Published: 01 November 2015 in Seizure
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PurposeOxidative stress is recognized as an important factor in progressive myoclonus epilepsy (PME). Genetic polymorphism of glutathione S-transferases (GSTs), which are involved in both protection from oxidative damage and detoxification, might alter the capacity for protecting tissues from exogenous and endogenous oxidants. We aimed to assess a possible association between GST polymorphism and PME, as well as, correlation between GST genotypes and oxidative phenotype in PME patients.MethodsGSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 26 patients with PME and 66 controls. Byproducts of protein oxidative damage (thiol groups (P-SH) and nitrotyrosine), superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were determined.ResultsThe frequency of GSTA1, GSTM1 and GSTP1 genotypes was not significantly different between PME patients and controls, while individuals with GSTT1-null genotype were at 5.44-fold higher risk of PME than carriers of GSTT1-active genotype. Moreover, significant risk of PME was obtained in carriers of both GSTT1-null and GSTM1-null genotypes. Carriers of combined GSTA1- active and GSTT1-null genotype were at highest, 7.55-fold increased risk of PME. Byproducts of protein damage did not reach statistical significance, while SOD and GPX activities were significantly higher in PME patients then in controls. When stratified according to GST genotype, P-SH groups were significantly lower only in patients with GSTT1-null genotype in comparison to carriers of active genotype. Only SOD activity was increased in GSTT1-null when compared to corresponding active genotype.ConclusionsGSTT1-null genotype might be associated with the increased risk and enhanced susceptibility to oxidative stress in PME patients

ACS Style

Marko Ercegovac; Nebojsa Jovic; Dragoslav Sokic; Ana Savic-Radojevic; Vesna Coric; Tanja Radic; Dimitrije Nikolic; Miljana Kecmanovic; Marija Matic; Tatjana Simic; Marija Pljesa-Ercegovac. GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case–control study. Seizure 2015, 32, 30 -36.

AMA Style

Marko Ercegovac, Nebojsa Jovic, Dragoslav Sokic, Ana Savic-Radojevic, Vesna Coric, Tanja Radic, Dimitrije Nikolic, Miljana Kecmanovic, Marija Matic, Tatjana Simic, Marija Pljesa-Ercegovac. GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case–control study. Seizure. 2015; 32 ():30-36.

Chicago/Turabian Style

Marko Ercegovac; Nebojsa Jovic; Dragoslav Sokic; Ana Savic-Radojevic; Vesna Coric; Tanja Radic; Dimitrije Nikolic; Miljana Kecmanovic; Marija Matic; Tatjana Simic; Marija Pljesa-Ercegovac. 2015. "GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case–control study." Seizure 32, no. : 30-36.

Journal article
Published: 08 August 2014 in Toxins
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Although recent data suggest aristolochic acid as a putative cause of Balkan endemic nephropathy (BEN), evidence also exists in favor of ochratoxin A (OTA) exposure as risk factor for the disease. The potential role of xenobiotic metabolizing enzymes, such as the glutathione transferases (GSTs), in OTA biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG) in blood and urine of BEN patients. We aimed to analyze the association between common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and thereafter performed an in silico simulation of particular GST enzymes potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1 genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals from endemic regions by polymerase chain reaction (PCR). Molecular modeling in silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of the GSTA1*B gene variant, associated with lower transcriptional activation, were at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A genotype (OR = 1.6; p = 0.037). In in silico modeling, we found four structures, two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1 polymorphism was associated with increased risk of BEN, and suggested, according to the in silico simulation, that GSTA1-1 might be involved in catalyzing the formation of OTHQ-SG and OTB-SG conjugates.

ACS Style

Zorica Reljic; Mario Zlatovic; Ana Savic-Radojevic; Tatjana Pekmezovic; Ljubica Djukanović; Marija Matic; Marija Pljesa-Ercegovac; Jasmina Mimić-Oka; Dejan Opsenica; Tatjana Simic. Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis. Toxins 2014, 6, 2348 -2362.

AMA Style

Zorica Reljic, Mario Zlatovic, Ana Savic-Radojevic, Tatjana Pekmezovic, Ljubica Djukanović, Marija Matic, Marija Pljesa-Ercegovac, Jasmina Mimić-Oka, Dejan Opsenica, Tatjana Simic. Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis. Toxins. 2014; 6 (8):2348-2362.

Chicago/Turabian Style

Zorica Reljic; Mario Zlatovic; Ana Savic-Radojevic; Tatjana Pekmezovic; Ljubica Djukanović; Marija Matic; Marija Pljesa-Ercegovac; Jasmina Mimić-Oka; Dejan Opsenica; Tatjana Simic. 2014. "Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis." Toxins 6, no. 8: 2348-2362.

Journal article
Published: 01 April 2013 in Journal of Medical Biochemistry
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Summary Background: To get more insight into the effects of the most widely used antiepileptic drugs (AEDs) on the prooxidant/ antioxidant balance in epilepsy, a comparative analysis of the byproducts of oxidative damage and antioxidant de fense mechanisms was performed in patients with epilepsy treated with lamotrigine, carbamazepine and valproic acid. Methods: Byproducts of oxidative damage to proteins (reactive carbonyl derivatives, RCD and protein thiol groups, PSH), lipids (urinary isoprostanes, 8-epi-PGF2a) and DNA (urinary 8-hydroxy-2’-deoxyguanosine, 8-OHdG), as well as the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured in 60 patients with newly diagnosed seizure (at illness onset and after 6 months of treatment with lamotrigine, carbamazepine or valproic acid) and in 20 healthy controls. Results: In patients with epilepsy, RCD, urinary 8-epi-PGF2a and 8-OHdG, together with SOD and GPX activities were significantly increased, while P-SH were only slightly decreased. After 6 months of treatment with AEDs, a decrease was observed in RCD, urinary 8-epi-PGF2a and 8-OHdG to values slightly higher or similar to the control, while P-SH remained unchanged. A decrease was also observed in SOD and GPX activities, although they remained significantly in creased compared to controls. Conclusions: The results of this study have shown that treatments with lamotrigine, carbamazepine and valproic acid affect the prooxidant/antioxidant balance in patients with epilepsy.

ACS Style

Marko Ercegovac; Nebojša Jović; Tatjana Simic; Ljiljana Beslać-Bumbaširević; Dragoslav Sokić; Ana Savic-Radojevic; Marija Matic; Dejana Jovanovic; Aleksandar Ristić; Tatjana Đukić; Sonja Suvakov; Vesna Coric; Jasmina Mimić-Oka; Marija Pljesa-Ercegovac. Antiepileptic Drugs Affect Protein, Lipid and DNA Oxidative Damage and Antioxidant Defense in Patients with Epilepsy. Journal of Medical Biochemistry 2013, 32, 121 -130.

AMA Style

Marko Ercegovac, Nebojša Jović, Tatjana Simic, Ljiljana Beslać-Bumbaširević, Dragoslav Sokić, Ana Savic-Radojevic, Marija Matic, Dejana Jovanovic, Aleksandar Ristić, Tatjana Đukić, Sonja Suvakov, Vesna Coric, Jasmina Mimić-Oka, Marija Pljesa-Ercegovac. Antiepileptic Drugs Affect Protein, Lipid and DNA Oxidative Damage and Antioxidant Defense in Patients with Epilepsy. Journal of Medical Biochemistry. 2013; 32 (2):121-130.

Chicago/Turabian Style

Marko Ercegovac; Nebojša Jović; Tatjana Simic; Ljiljana Beslać-Bumbaširević; Dragoslav Sokić; Ana Savic-Radojevic; Marija Matic; Dejana Jovanovic; Aleksandar Ristić; Tatjana Đukić; Sonja Suvakov; Vesna Coric; Jasmina Mimić-Oka; Marija Pljesa-Ercegovac. 2013. "Antiepileptic Drugs Affect Protein, Lipid and DNA Oxidative Damage and Antioxidant Defense in Patients with Epilepsy." Journal of Medical Biochemistry 32, no. 2: 121-130.

Journal article
Published: 01 June 2012 in Journal of Cardiac Failure
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Although the majority of previous findings unequivocally confirmed the existence of systemic oxidative stress in chronic heart failure (CHF) patients, data on prognostic potential of biomarkers of oxidative lipid and protein damage are limited. We aimed to address the relation of oxidative stress markers to severity and prognosis in CHF secondary to ischemic cardiomyopathy. Plasma malondialdehyde (MDA), protein thiol groups (P-SH), reactive carbonyl derivatives (RCD), together with glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined in 120 CHF patients and 69 healthy controls. Increased lipid peroxidation (MDA) and oxidation of plasma proteins (RCD; P-SH) s well as downregulated GSH-Px activity were found in CHF patients compared with controls. Significant correlation was obtained only for RCD content and remodeling indices (LVEDV: r = 0.469, P = .008; LVESV: r = 0.452; P = .011). Cox regression analysis demonstrated only MDA (HR = 3.33; CI: 1.55-7.12; P = .002) as independent predictor of death, whereas SOD was associated with unstable angina pectoris (HR = 2.09; CI: 1.16-3.78; P = .011). In the course of CHF progression, carbonyl stress is implicated in the LV remodeling. Malondialdehyde level might be a useful parameter for monitoring and planning management of CHF patients.

ACS Style

Slavica Radovanovic; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Tatjana Djukic; Sonja Suvakov; Mirjana Krotin; Dragan V. Simic; Marija Matic; Zoran Radojicic; Tatjana Pekmezovic; Tatjana Simic. Markers of Oxidative Damage and Antioxidant Enzyme Activities as Predictors of Morbidity and Mortality in Patients With Chronic Heart Failure. Journal of Cardiac Failure 2012, 18, 493 -501.

AMA Style

Slavica Radovanovic, Ana Savic-Radojevic, Marija Pljesa-Ercegovac, Tatjana Djukic, Sonja Suvakov, Mirjana Krotin, Dragan V. Simic, Marija Matic, Zoran Radojicic, Tatjana Pekmezovic, Tatjana Simic. Markers of Oxidative Damage and Antioxidant Enzyme Activities as Predictors of Morbidity and Mortality in Patients With Chronic Heart Failure. Journal of Cardiac Failure. 2012; 18 (6):493-501.

Chicago/Turabian Style

Slavica Radovanovic; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Tatjana Djukic; Sonja Suvakov; Mirjana Krotin; Dragan V. Simic; Marija Matic; Zoran Radojicic; Tatjana Pekmezovic; Tatjana Simic. 2012. "Markers of Oxidative Damage and Antioxidant Enzyme Activities as Predictors of Morbidity and Mortality in Patients With Chronic Heart Failure." Journal of Cardiac Failure 18, no. 6: 493-501.

Journal article
Published: 01 January 2011 in Srce i krvni sudovi
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Uvod: Istraživanja poslednjih nekoliko godina sugerišu da se hronična srčana insuficijencija (HSI) po- tencijalno može svrstati u veliku grupu oksidativnih oboljenja u čijem nastajanju i progresiji značajnu ulogu ima nekontrolisana produkcija slobodnih radikala. U ovom istraživanju su određivani pokazatelji oksidativnog oštećenja lipida i proteina kao i aktivnosti antioksidantnih enzima u plazmi bolesnika sa različitim stepenom HSI nakon infarkta miokarda. Analizirana je povezanost između markera oksidativ- nog stresa i pokazatelja remodelovanja leve komore. Metode: U istraživanje je uključeno 120 konsekutivnih bolesnika sa različitim stepenom HSI definisa- nim prema klasifikaciji Njujorškog kardiološkog društva (NYHA) i 69 zdravih ispitanika. Koncentracija malondialdehida u plazmi (MDA), proteinske tiol (P-SH) i reaktivne karbonilne grupe (RCD), zajedno sa aktivnošću glutation peroksidaze (GSH-Px) i superoksid dismutaze (SOD) određivani su spektrofoto- metrijski i/ili ELISA metodom i korelirani su sa ultrazvučnim indeksima remodelovanja, enddijastolnim i endsistolnim dimenzijama i volumenima (LVEDD, LVESD, LVEDV i LVESV). Rezultati: Kod bolesnika sa teškim stepenom HSI (NYHA klasa III/IV) izmerene su više koncentracije MDA i RCD i niži nivo P-SH grupa u odnosu na vrednosti zabeležene kod asimptomatskih bolesnika (NYHA klase I/II) ili kontrolne grupe. Oksidativni stres kod teških bolesnika bio je povezan sa značajnim padom aktivnosti GSH-Px u plazmi. Nađene su i značajne korelacije između sadržaja RCD i indeksa re- modelovanja, posebno volumena na kraju sistole (r=0,452; p= 0,011) i dijastole (r=0,469, p=0,008) ali samo kod bolesnika III i IV NYHA grupe. Zaključak: Pojačana peroksidacija lipida i oksidativno oštećenje proteina uz smanjene aktivnosti anti- oksidantnih enzima kod bolesnika sa teškim stepenom HSI ima važnu ulogu u nastanku sistemskog oksidativnog stresa kod ovih bolesnika, dok oksidativne modifikacije ključnih makromolekula imaju značajnu ulogu u remodelovanju leve komore u hroničnoj srčanoj insuficijenciji. Hronična srčana insuficijencija; oksidativni stres; koronarna bolest

ACS Style

Slavica Radovanović; Tatjana Đukić; Sonja Suvakov; Mirjana Krotin; Dragan V. Simić; Ana Savić-Radojević; Marija Plješa-Ercegovac; Aleksandra Đoković; Marija Matić; Nataša Janković; Tatjana Simić. Indicators of oxidative stress and plasma antioxidative enzyme activity in patients with different stages of heart failure. Srce i krvni sudovi 2011, 30, 35 -42.

AMA Style

Slavica Radovanović, Tatjana Đukić, Sonja Suvakov, Mirjana Krotin, Dragan V. Simić, Ana Savić-Radojević, Marija Plješa-Ercegovac, Aleksandra Đoković, Marija Matić, Nataša Janković, Tatjana Simić. Indicators of oxidative stress and plasma antioxidative enzyme activity in patients with different stages of heart failure. Srce i krvni sudovi. 2011; 30 (4):35-42.

Chicago/Turabian Style

Slavica Radovanović; Tatjana Đukić; Sonja Suvakov; Mirjana Krotin; Dragan V. Simić; Ana Savić-Radojević; Marija Plješa-Ercegovac; Aleksandra Đoković; Marija Matić; Nataša Janković; Tatjana Simić. 2011. "Indicators of oxidative stress and plasma antioxidative enzyme activity in patients with different stages of heart failure." Srce i krvni sudovi 30, no. 4: 35-42.

Journal article
Published: 01 April 2009 in Journal of Medical Biochemistry
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Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder is Associated with Down-Regulated CPP32 Expression and BCL-2 Positivity The objective was to get insight into the role of executive apoptotic enzyme caspase 3 (CPP32) and regulatory antiapoptotic protein Bcl-2 in the malignant phenotype of TCC. Samples were obtained from 84 TCC patients, who underwent transurethral resection, partial or radical cystectomy. Staging showed a superficial growth pattern in 41 patient, while other 43 showed invasive characteristics. Expression of CPP32 and Bcl-2 was determined by immunocytochemistry. Levels of expression were correlated with tumor stage and grade. Expression of CPP32 was positive in 80% of TCC patients. Low-, medium- and high positive status were observed in 18%, 24% and 38% of patients, respectively. There was a signifficant difference in the CPP32 expression between groups with superficial and invasive TCC tumors (p = 0.032), with frequency of CPP32 negative samples being higher and CPP32 high-positive samples being lower in patients with muscle-invasive tumors. Significant association was also found between CPP32 expression and tumor stage (p = 0.043). The positive rate of Bcl-2 protein expression was 48%. There was a statisticaly signifficant difference in the rate of Bcl-2 positivity between superficial and invasive TCC (p = 0.005), with frequency of Bcl-2 positive patients being higher in muscle-invasive TCC. Significant association was also found between Bcl-2 expression and both tumor grade (p=0.032) and stage (p=0.007). Muscle invasive TCC of the urinary bladder is associated with down-regulated expression of CPP32 and Bcl-2 positivity. Down-regulation of CPP32 and up-regulated Bcl-2 might, at least partially, play a role in the development of invasive characteristics of TCC.

ACS Style

Marija Pljesa-Ercegovac; Jasmina Mimić-Oka; Dejan Dragicevic; Ana Savic-Radojevic; Marija Matic; Tatjana Đukić; Tatjana Simic. Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder is Associated with Down-Regulated CPP32 Expression and BCL-2 Positivity. Journal of Medical Biochemistry 2009, 28, 101 -107.

AMA Style

Marija Pljesa-Ercegovac, Jasmina Mimić-Oka, Dejan Dragicevic, Ana Savic-Radojevic, Marija Matic, Tatjana Đukić, Tatjana Simic. Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder is Associated with Down-Regulated CPP32 Expression and BCL-2 Positivity. Journal of Medical Biochemistry. 2009; 28 (2):101-107.

Chicago/Turabian Style

Marija Pljesa-Ercegovac; Jasmina Mimić-Oka; Dejan Dragicevic; Ana Savic-Radojevic; Marija Matic; Tatjana Đukić; Tatjana Simic. 2009. "Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder is Associated with Down-Regulated CPP32 Expression and BCL-2 Positivity." Journal of Medical Biochemistry 28, no. 2: 101-107.

Journal article
Published: 01 July 2008 in Journal of Medical Biochemistry
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The Role of Glutathione S-Transferases in Urinary Tract Tumors Exposure to potential carcinogens is among the etiological factors for renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the urinary bladder. RCC is very resistant, while TCC exhibits a high recurrence rate and multifocality. Cytosolic glutathione S-transferases (GST) are a superfamily of enzymes which protect normal cells by catalyzing conjugation reactions between electrophylic compounds, including carcinogens, and glutathione. Some GST enzymes posses hydroperoxidase activity. The most well characterized classes have been named Alpha (GSTA), Mu (GSTM), Pi (GSTP) and Theta (GSTT) and each of these classes contains several different isoenzymes. Several types of allelic variation have been identified within classes, among which GSTM1-null and GSTT1-null confer impaired catalytic activity. Individuals with the GSTM1-null genotype carry a substantially higher risk for bladder carcinogenesis. The effects of glutathione S-transferase T1 polymorphism on the increased susceptibility to RCC and TCC of urinary bladder depend on the presence of specific chemical exposures to compounds metabolized via the GSTT1-1 pathway. In the process of kidney cancerisation expression of GST alpha isoenzymes tends to decrease, consequently favoring a prooxidant environment necessary for the growth of RCC. GST pi enzyme activities are generally retained in RCC and might contribute to the chemotherapy resistance of RCC. In the malignant phenotype of TCC of the urinary bladder up regulation of various GST classes occurs. Up regulation of GSTT1-1 and GSTP1-1 might have important consequences on the tumor growth, by providing a reduced environment and inhibition of apoptotic pathways.

ACS Style

Tatjana Simic; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Marija Matic; Tatjana Sašić; Dejan Dragicevic; Jasmina Mimić-Oka. The Role of Glutathione S-Transferases in Urinary Tract Tumors. Journal of Medical Biochemistry 2008, 27, 360 -366.

AMA Style

Tatjana Simic, Ana Savic-Radojevic, Marija Pljesa-Ercegovac, Marija Matic, Tatjana Sašić, Dejan Dragicevic, Jasmina Mimić-Oka. The Role of Glutathione S-Transferases in Urinary Tract Tumors. Journal of Medical Biochemistry. 2008; 27 (3):360-366.

Chicago/Turabian Style

Tatjana Simic; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Marija Matic; Tatjana Sašić; Dejan Dragicevic; Jasmina Mimić-Oka. 2008. "The Role of Glutathione S-Transferases in Urinary Tract Tumors." Journal of Medical Biochemistry 27, no. 3: 360-366.

Journal article
Published: 01 June 2008 in Redox Report
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We aimed to study the relationship between markers of oxidative lipid or protein damage and ventricular remodeling and the validity of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) as an indicator of disease severity in patients with ischemic chronic heart failure (CHF). We enrolled four groups of 12 patients with varying CHF according to the New York Heart Association (NYHA) classification and 25 controls. Urinary 8-epi-PGF(2alpha) and plasma malondialdehyde and protein thiol (P-SH) groups were correlated with echocardiographic indices of remodeling. The reliability of isoprostanes was analyzed by a receiver operating characteristics (ROC) curve. NYHA class III and IV patients exhibited elevated 8-epi-PGF(2alpha) levels, increased malondialdehyde concentrations and decreased P-SH groups when compared to controls and NYHA I and II patients. 8-Epi-PGF(2alpha) and P-SH groups correlated significantly with indices of remodeling. The ROC curve drawn for 8-epi-PGF(2alpha) allowed us to differentiate NYHA class III and IV patients from NYHA class I and II patients with a sensitivity of 95.8% and specificity of 95.8% (cut off 0.84 ng/mg creatinine; area under curve 0.99; P < 0.001). Markers of oxidative damage are unlikely to play a significant role in early stages of CHF. However, they might become important in the course of CHF when their concentrations reach critical levels. Urinary 8-epi-PGF(2alpha) is a reliable indicator of symptomatic CHF.

ACS Style

Slavica Radovanovic; Mirjana Krotin; Dragan V. Simic; Jasmina Mimic-Oka; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Marija Matic; Nebojsa Ninkovic; Branislava Ivanovic; Tatjana Simic. Markers of oxidative damage in chronic heart failure: role in disease progression. Redox Report 2008, 13, 109 -116.

AMA Style

Slavica Radovanovic, Mirjana Krotin, Dragan V. Simic, Jasmina Mimic-Oka, Ana Savic-Radojevic, Marija Pljesa-Ercegovac, Marija Matic, Nebojsa Ninkovic, Branislava Ivanovic, Tatjana Simic. Markers of oxidative damage in chronic heart failure: role in disease progression. Redox Report. 2008; 13 (3):109-116.

Chicago/Turabian Style

Slavica Radovanovic; Mirjana Krotin; Dragan V. Simic; Jasmina Mimic-Oka; Ana Savic-Radojevic; Marija Pljesa-Ercegovac; Marija Matic; Nebojsa Ninkovic; Branislava Ivanovic; Tatjana Simic. 2008. "Markers of oxidative damage in chronic heart failure: role in disease progression." Redox Report 13, no. 3: 109-116.