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Z Kovacević

Publications and source records attributed to Z Kovacević.

At least 19 recordsLinked to original sources
PubMed2002

[Application of tiazofurin in the study of regulation of AMP deaminase in intact malignant cells].

AMP deaminase has a key position in regulation of the pool of adenine nucleotides and energetics in malignant cells. The aim of this investigation was to elucidate mechanism of regulation of activity of AMP deaminase in intact tumor cells. Using tiazofurin, which profoundly decreases the level of GTP, and guanosine which markedly increases its concentration in the Ehrlich ascites tumor cells under aerobic conditions, we have shown that this nucleotide is probably the major regulator of AMP deaminase activity in situ. This regulation, however, should be considered in relation to the time and the changes which occur during transition of the cells from aerobic to anaerobic phase, and reverse, when other factors, like concentrations of the substrate and ATP are involved.

AMP Deaminase↗
PubMed1996

[Epidemiology of poststreptococcal glomerulonephritis in the military population].

Acute poststreptococcal glomerulonephritis appears often in children and our interest is the incidence of the disease in young adults (aged 18 to 22 years) especially in military people. In Nephrology Clinic of the Military Medical Academy (In the period from 1978 to the end of 1993) 153 patients were treated and sporadic cases developed after respiratory infection. Only 5 patients developed the disease after skin infection with Streptococcus B hemolyticus group A. A large number of patients acquired the disease in the period from February to April and from October to December and most of them in the time interval from 5 to 7 years. A substantial, number of patients were treated in 1982 (13), followed by 22 in 1989, and the trend continued in 1990 (24 patients) while only 6 patients presented in 1993. So, the incidence of the disease in the military population is not high (10 +/- 6 patients year and it was sporadic cases and more after respiratory infection.

Adolescent↗
PubMed1996

[Correlation of inflammatory cytokines in the urine and serum with clinico-laboratory and pathohistologic features in patients with IgA nephropathy].

Complete examination of 21 patients with IgA nephropathy included determination urine and serum IL-6, TNF alpha and INF gamma levels by ELISA (Luzernachen, Luzern Switzerland). Control group included 15 healthy volunteers. Urine IL-6 levels ranging 37-274.1 pg/ml were detected in 15 (71.2%) patients with IgA nephropathy. IL-6 serum levels were undetectable. In the control group serum and urine levels were also undetectable. Correlation between the IL-6 level and proteinuria degree and endogenous creatinine clearance rate has not revealed statistically significant relationship. In relation to histologic groups (minimal changes, focal glomerulonephritis, mesangial proliferative, diffuse sclerosing) patients with minimal changes had (statistically) significantly higher IL-6 urine levels than the third and fourth group. Average the urine levels were 145.8 +/- 166.6 pg/ml and the serum ones were 148 +/- 101 pg/ml. In relation to the control group (statistically) significant difference was not found. Correlation between TNF alpha level and proteinuria degree and creatinine clearance rate has revealed (statistically) significant relationship (p < 0.05). Average interferon gamma serum levels in lgA nephropathy patients were 312.0 +/- 111.8 and in comparison with the control group (statistically) significant difference was found (p < 0.01). The obtained results suggest the important role of cytokine production disregulation associated with the pathogenesis of IgA nephropathy.

Adolescent↗
PubMed1996

[Nephrotic proteinuria in poststreptococcal glomerulonephritis].

Nephrotic proteinuria in acute poststreptococcal glomerulonephritis is rare. In 62 patients aging from 18 to 22 years, proteinuria of > 3 g/24 hrs was found ins 5 (8%) patients, 0.3 to 3 g/24 hrs in 36 (58%) and 0.15 to 0.3 g/24 hrs in 21 (34%) patients. Proteinuria in many patients disappeared after 3 months and in later follow up it was found in about 30% of patients. Out of 5 patients with proteinuria of > 3 g/24 hrs 3 had persistent pathological urinary analysis, 2 patients were rebiopsied after 5 and 3 years from the disease onset, the morphological changes were moderate. In 2 patients after acute phase had been over came to the clinical healthy (with normal urinary analysis) lasting for 2 years and in the rebiopsy less marked pathological changes were described. Immunofluorescent analysis in the all patients were negative. Patients with initial nephrotic proteinuria in poststreptococcal glomerulonephritis have bad prognosis and often develop chronic disease.

Acute Disease↗
PubMed1991

Control and function of the transamination pathways of glutamine oxidation in tumour cells.

Parallel investigations of the transamination pathways of glutamine oxidation in Ehrlich ascites carcinoma (EAC) and AS 30D hepatoma revealed that hepatoma cells, unlike EAC, produce very little aspartate. This cannot be explained by differences in the activity of glutamine-metabolizing enzymes. Also, the mitochondria from the hepatoma respired at a similar rate to EAC mitochondria with glutamine as sole substrate producing substantial amounts of aspartate. Unlike their isolated mitochondria, intact hepatoma cells showed a very low rate of glutamine oxidation. Compared with EAC, the rate of L-[U-14C]glutamine consumption by AS 30D hepatoma cells was much lower, with insignificant production of 14C-labelled aspartate and CO2. This suggested that the glutamine-transporting system in the hepatoma cell plasma membrane had a very low activity. Isolated hepatoma mitochondria produced 3 times more pyruvate from malate than did EAC mitochondria, indicating a higher activity of NAD(P)-dependent malic enzyme. We postulate that an active malic enzyme may suppress the synthesis of aspartate in hepatoma cells, but further evidence is needed to confirm this assumption.

Alanine↗
PubMed1991

Mechanism and control of degradation and resynthesis of adenylates in tumour cells.

A comparative study revealed that Ehrlich ascites carcinoma (EAC) cells use glutamine plus inosine for regeneration of adenylates via the purine nucleotide cycle, whereas AS 30D hepatoma cells use adenosine instead. This observation can be correlated with the very low production of aspartate from glutamine in hepatoma cells. Although glucose is an important energy fuel for EAC, it cannot maintain a high enough level of adenylates unless glutamine is also present. Kinetic analysis of hydrolysis of ATP and ADP in the presence of rotenone suggests that deamination of AMP does not maintain a high enough ATP/ADP ratio and probably does not act as energy buffer after inhibition of cell respiration. It seems that, compared with normal cells, malignant cells have the ability for a very rapid regeneration of adenylates. It is proposed that instability of the adenine nucleotide pool, owing to frequent aerobic-anaerobic transitions, represents an essential feature of neoplasia, with profound impact on the whole metabolism of tumour cells.

Adenine Nucleotides↗
PubMed1990

[Kinetics of degradation and resynthesis of the adenine-nucleotide pool in tumor cells].

Starting from the assumption that tumor cells constantly experience transient ischemia and anoxia, and that this results in metabolic stress which is reflected above all, on the concentration of ATP, ADP and AMP, in other words, the adenine nucleotide pool (AdN), the aim of our research was to study the degradation and resynthesis kinetics of that pool on two types of malignant cells. All experiments were conducted in vitro with cells of the transplantable tumors of Ehrlich's ascitic carcinoma and the AS 30D hepatoma, and metabolite analyses were carried out enzymatically or by way of the HPLC chromatography method. It was found that immediately after the setting on of anoxia, there comes not only to a fall in ATP, but also to a fall in the complete adenine nucleotide pool for about 50%. The further maintenance of anaerobiosis does not have a significant influence on the AdN pool. The adenine nucleotide pool resynthesis is very rapid in the examined cells, and in the presence of glutamine and inosine, there comes to an occurrence of its significant growth. Evidence is given that the resynthesis in Ehrlich's ascitic carcinoma cells is made possible through the purine nucleotide cycle, which probably brings about the intensive glutamine oxidation and aspartate production, while in the AS 30D hepatoma cells it develops by means of adenosine kinase. The AS 30D hepatoma cells maintain a high ATP level in the absence of oxygen for a long time, provided that iodine-acetate is not added, which points to the fact that they have some other kind of energetic reserve aside from ATP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1988

The role of glutamine oxidation and the purine nucleotide cycle for adaptation of tumour energetics to the transition from the anaerobic to the aerobic state.

It is proposed that the purine nucleotide cycle and glutamine oxidation play a key role in the adaptation of tumour energetics to the transition from the anaerobic to the aerobic state. In support of this proposal, it was found that glutamine and inosine markedly increase total adenylates in the presence of oxygen, whereas the addition of hadacidin abolishes this effect. Transition of the cells from the anaerobic to the aerobic state, and vice versa, in the presence of glutamine plus inosine revealed that there are two components of the adenine nucleotide pool, one which is stable and the other which is variable and responds to the aerobic-anaerobic transition. This part of the pool undergoes degradation or resynthesis owing to activation of the enzymes of the purine nucleotide cycle. Resynthesis of the pool is accompanied by substantial net utilization of aspartate, which is produced by glutamine oxidation. This is supported by the experiments in which the cells were alternately incubated with nitrogen or oxygen, demonstrating that hadacidin significantly decreased utilization of aspartate and regeneration of ATP owing to inhibition of adenylosuccinate synthase.

Adenine Nucleotides↗
PubMed1987

Interaction of metabolism of aspartate and inosine and energy state of malignant cells.

1. Oxidation of glutamine in Ehrlich ascites-carcinoma cells results in a large accumulation of aspartate. 2. The addition of inosine causes a marked decrease in aspartate production from glutamine. This may be related to the resynthesis of AMP from aspartate and IMP, the latter being produced from inosine via the salvage pathway for purine nucleotides. In accordance with this assumption, a significant production of lactate was observed, which comes probably from the ribose moiety of inosine. Since lactate is known to inhibit production of aspartate from glutamine, this may explain the effect of inosine. 3. Addition of glutamine together with inosine increased cellular ATP content. This was not the case if glutamine or inosine was present separately or if inosine was added together with lactate, pyruvate or glucose. The effect did not occur if amino-oxyacetate, an inhibitor of transaminases, was added. These findings suggested again that production of aspartate is important for resynthesis of ATP from IMP via the purine nucleotide cycle. 4. If the cells were exposed to prolonged anaerobic incubation, addition of glutamine and inosine markedly increased O2 uptake and [ATP], suggesting the crucial importance of aspartate production by glutamine oxidation for the recovery of energy metabolism in the cells.

Adenosine Triphosphate↗
PubMed1982

Kinetics of glutamine-efflux from liver mitochondria loaded with the 14C-Labeled substrate.

Glutamine transport across the inner membrane of rat liver mitochondria was studied by the method of loading the organelles with [14C]glutamine and by measuring efflux of the metabolite at 0 degree C. The release of [14C]glutamine from loaded mitochondria was prevented by mersalyl, whereas the efflux was started by the addition of glutathione. The rate of glutamine efflux from the mitochondria was measured by the inhibitor stop technique with mersalyl plus N-ethylmaleimide. It was found that up to 10 mM glutamine there is no significant activity of glutaminase, whereas at about 20 mM of the substrate the enzyme is activated. The rate of the efflux measured after the addition of the optimal amount of glutathione was 10 nmol glutamine/min per mg protein. This is 5-times faster than the rate of glutaminase activity at 0 degree C. The pH optimum of glutamine carrier is between 6.5 and 7.0. Low concentration of succinate inhibits the efflux due to formation of pH gradient in coupled mitochondria, whereas a higher concentration of succinate inhibits the carrier directly. 2-Oxoglutarate and glutamate strongly inhibit the rate of glutamine efflux, the inhibition by glutamate being very pronounced at its physiological concentration. D-Glutamine does not inhibit the rate of the efflux, indicating that the transport of L-glutamine is stereospecific.

Animals↗