Publications by authors named "Jelena Tasic"

8 Publications

  • Page 1 of 1

Role of AMPK/mTOR-independent autophagy in clear cell renal cell carcinoma.

J Investig Med 2020 12 21;68(8):1386-1393. Epub 2020 Oct 21.

Institute of Microbiology and Immunology, University of Belgrade Faculty of Medicine, Belgrade, Serbia

We examined the status and role of autophagy, a process of lysosomal recycling of cellular material, in clear cell renal cell carcinoma (ccRCC). Paired samples of tumor and adjacent non-malignant tissue were collected from 20 patients with ccRCC after radical nephrectomy. The mRNA levels of apoptosis (, , , , ) and autophagy (, , , , ) regulators were measured by RT-qPCR. The protein levels of autophagosome-associated LC3-II, autophagy receptor p62, apoptotic marker PARP, as well as phosphorylation of autophagy initiator Unc 51-like kinase 1 (ULK1), its activator AMP-activated protein kinase (AMPK) and 4EBP1, the substrate of ULK1 inhibitor mechanistic target of rapamycin (mTOR), were analyzed by immunoblotting. The mRNA levels of pro-apoptotic , anti-apoptotic and pro-autophagic , and were higher in ccRCC tumors. Autophagy induction was confirmed by an increase in phospho-ULK1 and degradation of the autophagic target p62, while apoptotic PARP cleavage was unaltered. AMPK phosphorylation was reduced and 4EBP1 phosphorylation was increased in ccRCC tissue. The expression of apoptosis regulators did not correlate with clinicopathological features of ccRCC. Conversely, high mRNA levels of and were associated with lower tumor stage, as well as with smaller tumor size and better disease-specific 5-year survival ( and ). Accordingly, low p62 protein levels, corresponding to increased autophagic flux, were associated with lower tumor stage, reduced metastasis and improved 5-year survival. These data demonstrate that transcriptional induction of autophagy in ccRCC is accompanied by AMPK/mTOR-independent increase in ULK1 activation and autophagic flux, which might slow tumor progression and metastasis independently of apoptosis.
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http://dx.doi.org/10.1136/jim-2020-001524DOI Listing
December 2020

Influence of preoperative statins and aspirin administration on biological and magnetic resonance imaging properties in patients with abdominal aortic aneurysm.

Vasa 2021 Feb 16;50(2):116-124. Epub 2020 Jul 16.

School of Medicine, University of Belgrade, Serbia.

: Main objective of this study was to evaluate the influence of statins and/or acetylsalicylic acid on biochemical characteristics of abdominal aortic aneurysm (AAA) wall and intraluminal thrombus (ILT). : Fifty patients with asymptomatic infrarenal AAA were analyzed using magnetic resonance imaging on T1w sequence. Relative ILT signal intensity (SI) was determined as a ratio between ILT and psoas muscle SI. Samples containing the full ILT thickness and aneurysm wall were harvested from the anterior surface at the level of the maximal diameter. The concentration of enzymes such as matrix metalloproteinase (MMP) 9, MMP2 and neutrophil elastase (NE/ELA) were analyzed in ILT and AAA wall; while collagen type III, elastin and proteoglycan 4 were analyzed in harvested AAA wall. Oxidative stress in the AAA wall was assessed by catalase and malondialdehyde activity in tissue samples. : Relative ILT signal intensity (1.09 ± 0.41 vs 0.89 ± 0.21, p = 0.013) were higher in non-statin than in statin group. Patients who were taking aspirin had lower relative ILT area (0.89 ± 0.19 vs 1.13. ± 0.44, p = 0.016), and lower relative ILT signal intensity (0.85 [0.73-1.07] vs 1.01 [0.84-1.19], p = 0.021) compared to non-aspirin group. There were higher concentrations of elastin in AAA wall among patients taking both of aspirin and statins (1.21 [0.77-3.02] vs 0.78 (0.49-1.05) ng/ml, p = 0.044) than in patients who did not take both of these drugs. : Relative ILT SI was lower in patients taking statin and aspirin. Combination of antiplatelet therapy and statins was associated with higher elastin concentrations in AAA wall.
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http://dx.doi.org/10.1024/0301-1526/a000895DOI Listing
February 2021

Identification of a functional protein kinase Cbeta promoter polymorphism in humans related to insulin resistance.

Mol Genet Metab 2008 Feb 22;93(2):210-5. Epub 2007 Oct 22.

German Institute of Human Nutrition, Potsdam-Rehbruecke (DIfE), Department of Clinical Nutrition (KLE), Arthur-Scheunert-Allee 155, D-14558 Nuthetal, Germany.

Protein kinase Cbeta (PKCbeta) is known to inhibit insulin production in beta-cells and to support insulin action in skeletal muscle. We therefore searched for functional polymorphisms among already known genetic variants in the PKCbeta promoter and investigated their relation to glucose metabolism in humans. We found that the gene variant in the PKCbeta promoter at position -546 significantly reduced promoter activity in functional assays (P<0.05). Human subjects carrying this variant had a 3.5-fold decrease in PKCbeta2-protein expression in their thrombocytes (P=0.006). Additionally, we tested whether this variant affects parameters of glucose metabolism using 1012 humans included into the MeSyBePo study (Metabolic Syndrome Berlin Potsdam). The -546 variant was highly significant associated with increased homeostasis model assessment for insulin resistance (HOMA-IR, P=0.009) in the cohort. This association was accompanied by significantly increased fasting insulin concentrations in carriers of the homozygous polymorphism (P=0.021). Our results suggest that the -546 polymorphism in the PKCbeta promoter reduces promoter activity, which leads to a decreased expression of PKCbeta2 and subsequently is associated with decreased peripheral insulin-dependent glucose uptake.
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http://dx.doi.org/10.1016/j.ymgme.2007.09.004DOI Listing
February 2008

Synthesis and biological activity of some new 5'-O-acyl tiazofurin derivatives.

Eur J Med Chem 2006 Apr 7;41(4):503-12. Epub 2006 Mar 7.

Department of Chemistry, Faculty of Sciences, University of Novi Sad, Serbia & Montenegro.

Three new 5'-O-acyl tiazofurin derivatives 2-4 were synthesized and evaluated for their antiproliferative activity against different tumour cell lines as well as for their ability to induce apoptosis in C6 cells in vitro. Apart of the antitumour assays, the cell membrane permeation of 2-4 and their intracellular metabolism in C6 cells in vitro was also studied in order to evaluate their potential as possible tiazofurin bioisosteres or prodrugs.
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http://dx.doi.org/10.1016/j.ejmech.2006.01.005DOI Listing
April 2006

The effects of tiazofurin on basal and amphetamine-induced motor activity in rats.

Pharmacol Biochem Behav 2004 Mar;77(3):575-82

Laboratory of Electrophysiology and Behaviour, Department of Neurobiology and Immunology, Institute for Biological Research, 29th November 142, 11060 Belgrade, Serbia and Montenegro.

The effects of tiazofurin (TR; 2-beta-d-ribofuranosylthiazole-4-carboxamide), a purine nucleoside analogue on basal and amphetamine (AMPH)-induced locomotor and stereotypic activity of adult Wistar rat males were studied. The animals were injected with low (3.75, 7.5, and 15 mg/kg ip) and high (62.5, 125, and 250 mg/kg ip) TR doses. Neither low nor high TR doses influenced basal locomotor and stereotypic activity in comparison with the corresponding controls treated with saline only. However, pretreatment with TR at any dose applied, except for the lowest one, significantly decreased AMPH-induced (1.5 mg/kg ip) locomotor activity, while AMPH-induced stereotypic activity was inhibited with the two highest TR doses. In addition, TR was detected in the brain by HPLC already 15 min after the injection (125 mg/kg ip) to reach a maximum 2 h after the administration and was detectable in this tissue during the next 4 h. Our results indicate that TR modifies central regulation of the motor activity, possibly by influencing dopaminergic (DA-ergic) transmission.
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http://dx.doi.org/10.1016/j.pbb.2003.12.025DOI Listing
March 2004

HPLC determination of tiazofurin in the rat brain.

J Pharm Biomed Anal 2003 Nov;33(4):839-43

Galenika a.d. Institute, Center for Biomedical Research, Belgrade, Serbia and Montenegro.

A sensitive, selective and reproducible HPLC method for determination of tiazofurin in rat brain was developed and validated. The method allowed determination and quantification of nanomolar concentrations of tiazofurin in brain and its regions (hippocampus, cortex and striatum) of treated animals. Separation of tiazofurin from other peaks from brain tissue was achieved by isocratic elution on reverse phase chromatographic column. The mobile phase consisted of 0.05 M sodium acetate pH 4.6. Run time was 15 min.
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http://dx.doi.org/10.1016/j.japna.2003.06.001DOI Listing
November 2003

The linkage of glucose to tiazofurin decreases in vitro uptake into rat glioma C6 cells.

J Drug Target 2002 Dec;10(8):633-6

ICN Galenika, R and D, Belgrade, Federal Republic of Yugoslavia.

The aim of this study was to analyse the uptake of the synthetic nucleoside tiazofurin and glucoso-linker-tiazofurin conjugate (GLTC) into rat C6 glioma cells in vitro. Results indicated that C6 cells accumulated [3H] tiazofurin slowly with time and that accumulation was reduced by the presence of unlabelled GLTC in the medium which implies that GLTC competes with tiazofurin for transport sites. Uptake of [14C] 2 deoxy-glucose into these cells was very rapid and was not affected by the presence of unlabelled GLTC. To prove the true rate of uptake, the HPLC analysis of cellular extract was performed. After the 360 min of incubation in medium that contained 0.15 mM of tiazofurin, the sum of the concentration of tiazofurin and it's metabolite thiazole-adenine dinucleotide (TAD) in the cells was a total of approximately 4.8% of the amount added to each flask. After the same period of incubation in medium which contained 0.15 mM of GLTC, the sum of concentrations of conjugate, free tiazofurin and TAD represented less than 1/3 of the total concentration measured after the incubation with free tiazofurin and was further reduced in the presence of dipyridamole. Therefore, it can be concluded that GLTC shows some affinity for the nucleoside transporter, but the actual rate of uptake is low.
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http://dx.doi.org/10.1080/1061186021000038030DOI Listing
December 2002

Simultaneous LC determination of tiazofurin, its acetyl and benzoyl esters and their active metabolite thiazole-4-carboxamide adenine dinucleotide in biological samples.

J Pharm Biomed Anal 2002 Nov;30(4):993-9

ICN Galenika Institute, Center for Biomedical Research, Pasterova 2, 11000, Belgrade, Yugoslavia.

A rapid and sensitive HPLC-RP method for simultaneous determination of tiazofurin, its 5'-O acetyl and benzoyl esters and their active metabolite thiazole-4-carboxamide adenine dinucleotide was developed and validated. The method allowed determination and quantification of nanomolar quantities of these substances in cell extracts of treated cells, and was also used in kinetic studies of cellular uptake of tiazofurin and its esters from the cultivation medium. Separation of the analyzed substances from unidentified peaks from both biological materials was achieved by gradient elution, thus reducing the possibility of interference. The mobile phase consisted of a 0.1 M sodium-hydrogen phosphate, pH 5.1 and methanol. Run time was 22 min, with 5 min equilibration time.
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http://dx.doi.org/10.1016/s0731-7085(02)00448-xDOI Listing
November 2002
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